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Sample records for common genetic control

  1. Common genetic variation and the control of HIV-1 in humans

    DEFF Research Database (Denmark)

    Fellay, J.; Ge, D.; Shianna, K.V.

    2009-01-01

    To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. ...... genetic variation in HIV-1 control in Caucasians Udgivelsesdato: 2009/12......To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We...

  2. Genetic control of the angular leaf spot reaction in common bean leaves and pods

    Directory of Open Access Journals (Sweden)

    Jerônimo Constantino Borel

    2011-12-01

    Full Text Available Information about genetic control of plant reaction to pathogens is essential in plant breeding programs focusing resistance. This study aimed to obtain information about genetic control of the angular leaf spot reaction in leaves and pods from common bean (Phaseolus vulgaris L. line ESAL 686. This line was crossed with cultivars Jalo EEP 558 (resistant, Cornell 49-242 (resistant and Carioca MG (susceptible. Generations F1, F2 and backcrosses (BC11 and BC21 were obtained. In the dry season (2009, parents and respective populations were evaluated for angular leaf spot reaction under field conditions. Disease severity was evaluated on leaves and pods using diagrammatic scales. Severity scores were obtained and mean and variance genetic components were estimated for both. Segregation of F2 generation was analyzed for some crosses. Different genes control angular leaf spot reaction in leaves and pods. Mean and variance components showed predominance of additive effects. Heritability was high, however, was greater on pods than on leaves which indicated that leaf reaction is more influenced by the environment.

  3. Genetic evidence that Drosophila frizzled controls planar cell polarity and Armadillo signaling by a common mechanism.

    Science.gov (United States)

    Povelones, Michael; Howes, Rob; Fish, Matt; Nusse, Roel

    2005-12-01

    The frizzled (fz) gene in Drosophila controls two distinct signaling pathways: it directs the planar cell polarization (PCP) of epithelia and it regulates cell fate decisions through Armadillo (Arm) by acting as a receptor for the Wnt protein Wingless (Wg). With the exception of dishevelled (dsh), the genes functioning in these two pathways are distinct. We have taken a genetic approach, based on a series of new and existing fz alleles, for identifying individual amino acids required for PCP or Arm signaling. For each allele, we have attempted to quantify the strength of signaling by phenotypic measurements. For PCP signaling, the defect was measured by counting the number of cells secreting multiple hairs in the wing. We then examined each allele for its ability to participate in Arm signaling by the rescue of fz mutant embryos with maternally provided fz function. For both PCP and Arm signaling we observed a broad range of phenotypes, but for every allele there is a strong correlation between its phenotypic strength in each pathway. Therefore, even though the PCP and Arm signaling pathways are genetically distinct, the set of signaling-defective fz alleles affected both pathways to a similar extent. This suggests that fz controls these two different signaling activities by a common mechanism. In addition, this screen yielded a set of missense mutations that identify amino acids specifically required for fz signaling function.

  4. Genetic control of common bean (Phaseolus vulgaris resistance to powdery mildew (Erysiphe polygoni

    Directory of Open Access Journals (Sweden)

    Rezende Viviane Ferreira

    1999-01-01

    Full Text Available Genetic control of common bean (Phaseolus vulgaris resistance to powdery mildew (Erysiphe polygoni was studied using segregating populations from the bean variety crosses Jalo x ESAL 686 and ESAL 550 x ESAL 686. F2 plants, together with the parents, were inoculated and evaluated using a scale of values from one (plant without symptoms to nine (completely infected plant. F2 plants were harvested individually, and F2:3 families were obtained. These families were evaluated in an 11 x 11 and 12 x 12 simple lattice statistical design for the Jalo x ESAL 686 and ESAL 550 x ESAL 686 crosses, respectively, using the same value scale as the F2 generation. The segregation observed in F2 plants and F2:3 families indicated that two genes are involved in genetic control, due to a double recessive epistasis. The high linear regression coefficient (b between F2 plants and their F2:3 family, 0.66 for ESAL 550 x ESAL 686 cross, and 0.71 for Jalo x ESAL 686 cross, showed that the trait is highly heritable.

  5. Genetic control of the number of days to flowering in common bean

    Directory of Open Access Journals (Sweden)

    Marcela Pedroso Mendes

    2008-01-01

    Full Text Available The aim of this study was to investigate the genetic control of early flowering in common bean. Crosses weremade between the parents Pérola and BRS Radiante and between ESAL 506 and Preto 60 dias. The segregating generations,F3, F2BC11 and F2BC12 of each cross were evaluated in experiments with two replications. F3 plants of both crosses wererandomly taken, and F3:4 progenies evaluated for the trait number of days to flowering. There was good adjustment to theadditive-dominant model of both crosses. The dominance effect was lower than the additive effect in the trait control and, whenpresent, it reduced the number of days to flowering. The value of realized heritability (h2R was similar in both crosses andlower than the h2 estimated for selection among F3:4 progenies. There were indications that aside from the environmental effecton the trait expression, the genotype-environment interaction was also significant.

  6. Genetic control on the performance of common bean differential cultivars to Colletotrichum lindemuthianum races

    Directory of Open Access Journals (Sweden)

    Maria Celeste Gonçalves-Vidigal

    2007-07-01

    Full Text Available The aim of this work was to perform genetic control on differential cultivars Michelite, Michigan Dark Red Kidney, Perry Marrow, Cornell 49-242, PI 207262, AB 136 and G 2333 and its diallel hybrids by using Hayman's methodology. The entire F1s populations were evaluated in relation to race 89, whereas the race 31, the diallel scheme did not include the cultivar G 2333. The results showed that the additive effects were predominant for the 31 race, while non-additive effects were more important for race 89. The results demonstrated a high coefficient of genetic determination for the race 31. The G 2333, AB 136 and PI 207262 cultivars should be recommended obtaining cultivar resistant to anthracnose by backcross programs because theyshowed the highest proportion of resistant dominant alleles for the races 31 and 89.Dentre as várias doenças que causam problemas no cultivo de feijão comum (Phaseolus vulgaris L., uma das mais importantes é a antracnose causada pelo fungo Colletotrichum lindemuthianum (Saac. et Magn. Scrib., a qual pode resultar em severas perdas na produtividade de grãos. O controle genético, nas cultivares diferenciais Michelite, Michigan Dark Red Kidney, Perry Marrow, Cornell 49-242, PI 207262, AB 136 e G 2333 e seus 21 híbridos dialélicos, foi obtido usando a metodologia de Hayman (1954. Todas as populações F1s foram avaliadas em relação à raça 89, enquanto que os híbridos envolvendo a cultivar G 2333 não foram avaliados com a raça 31. Os resultados demonstraram que os efeitos aditivos foram predominantes para a raça 31, enquanto os efeitos gênicos não aditivos foram mais importantes na reação de incompatibilidade das cultivares a raça 89. Os resultados ainda evidenciaram um elevado coeficiente de determinação genética para a raça 31. Os cultivares G 2333, AB 136 e PI 207262 são os mais indicados para programas de melhoramento visando à obtenção de cultivares resistentes à antracnose por possu

  7. Statistical Colocalization of Genetic Risk Variants for Related Autoimmune Diseases in the Context of Common Controls

    Science.gov (United States)

    Fortune, Mary D.; Guo, Hui; Burren, Oliver; Schofield, Ellen; Walker, Neil M.; Ban, Maria; Sawcer, Stephen J.; Bowes, John; Worthington, Jane; Barton, Ann; Eyre, Steve; Todd, John A.; Wallace, Chris

    2015-01-01

    Identifying whether potential causal variants for related diseases are shared can identify overlapping etiologies of multifactorial disorders. Colocalization methods disentangle shared and distinct causal variants. However, existing approaches require independent datasets. Here we extend two colocalization methods to allow for the shared control design commonly used in comparison of genome-wide association study results across diseases. Our analysis of four autoimmune diseases, type 1 diabetes (T1D), rheumatoid arthritis, celiac disease and multiple sclerosis, revealed 90 regions that were associated with at least one disease, 33 (37%) of which with two or more disorders. Nevertheless, for 14 of these 33 shared regions there was evidence that causal variants differed. We identified novel disease associations in 11 regions previously associated with one or more of the other three disorders. Four of eight T1D-specific regions contained known type 2 diabetes candidate genes: COBL, GLIS3, RNLS and BCAR1, suggesting a shared cellular etiology. PMID:26053495

  8. Age at Onset in Two Common Neurodegenerative Diseases Is Genetically Controlled

    Science.gov (United States)

    Li, Yi-Ju; Scott, William K.; Hedges, Dale J.; Zhang, Fengyu; Gaskell, P. Craig; Nance, Martha A.; Watts, Ray L.; Hubble, Jean P.; Koller, William C.; Pahwa, Rajesh; Stern, Matthew B.; Hiner, Bradley C.; Jankovic, Joseph; Allen, Jr., Fred H.; Goetz, Christopher G.; Mastaglia, Frank; Stajich, Jeffrey M.; Gibson, Rachel A.; Middleton, Lefkos T.; Saunders, Ann M.; Scott, Burton L.; Small, Gary W.; Nicodemus, Kristin K.; Reed, Allison D.; Schmechel, Donald E.; Welsh-Bohmer, Kathleen A.; Conneally, P. Michael; Roses, Allen D.; Gilbert, John R.; Vance, Jeffery M.; Haines, Jonathan L.; Pericak-Vance, Margaret A.

    2002-01-01

    To identify genes influencing age at onset (AAO) in two common neurodegenerative diseases, a genomic screen was performed for AAO in families with Alzheimer disease (AD; n=449) and Parkinson disease (PD; n=174). Heritabilities between 40%–60% were found in both the AD and PD data sets. For PD, significant evidence for linkage to AAO was found on chromosome 1p (LOD = 3.41). For AD, the AAO effect of APOE (LOD = 3.28) was confirmed. In addition, evidence for AAO linkage on chromosomes 6 and 10 was identified independently in both the AD and PD data sets. Subsequent unified analyses of these regions identified a single peak on chromosome 10q between D10S1239 and D10S1237, with a maximum LOD score of 2.62. These data suggest that a common gene affects AAO in these two common complex neurodegenerative diseases. PMID:11875758

  9. Genetic determinants of common epilepsies

    DEFF Research Database (Denmark)

    2014-01-01

    and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilepsy and focal epilepsy). METHODS: We combined genome-wide association data from 12 cohorts of individuals with epilepsy...... and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different...... genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance...

  10. Association study of common genetic variants and HIV-1 acquisition in 6,300 infected cases and 7,200 controls

    DEFF Research Database (Denmark)

    McLaren, Paul J; Coulonges, Cédric; Ripke, Stephan

    2013-01-01

    Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although...... that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed...... no evidence for genetic influence on HIV-1 acquisition (with the exception of CCR5Δ32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size....

  11. Genetic control of the fungus Colletotrichum lindemuthianum (Sacc. & Magn.) Scrib. reaction and corona color in the common bean (Phaseolus vulgaris L.)

    OpenAIRE

    MENDONÇA, H. A. de.; dos Santos, J.B.; Ramalho,M.A.P.; FERREIRA, D.F.

    1998-01-01

    An important trait for common bean (Phaseolus vulgaris L.) cultivars with Carioca type grain is resistance to Colletotrichum lindemuthianum, which causes anthracnose and a pale corona. The present study was conducted to understand the genetic control of common bean reaction to the fungus and of the corona color, to provide guides to future breeding studies. Genotypes P-45, with brown corona, and EMGOPA 201-Ouro, with yellow corona, are resistant to C. lindemuthianum. Cultivar Carioca is susce...

  12. Common Control System Vulnerability

    Energy Technology Data Exchange (ETDEWEB)

    Trent Nelson

    2005-12-01

    The Control Systems Security Program and other programs within the Idaho National Laboratory have discovered a vulnerability common to control systems in all sectors that allows an attacker to penetrate most control systems, spoof the operator, and gain full control of targeted system elements. This vulnerability has been identified on several systems that have been evaluated at INL, and in each case a 100% success rate of completing the attack paths that lead to full system compromise was observed. Since these systems are employed in multiple critical infrastructure sectors, this vulnerability is deemed common to control systems in all sectors. Modern control systems architectures can be considered analogous to today's information networks, and as such are usually approached by attackers using a common attack methodology to penetrate deeper and deeper into the network. This approach often is composed of several phases, including gaining access to the control network, reconnaissance, profiling of vulnerabilities, launching attacks, escalating privilege, maintaining access, and obscuring or removing information that indicates that an intruder was on the system. With irrefutable proof that an external attack can lead to a compromise of a computing resource on the organization's business local area network (LAN), access to the control network is usually considered the first phase in the attack plan. Once the attacker gains access to the control network through direct connections and/or the business LAN, the second phase of reconnaissance begins with traffic analysis within the control domain. Thus, the communications between the workstations and the field device controllers can be monitored and evaluated, allowing an attacker to capture, analyze, and evaluate the commands sent among the control equipment. Through manipulation of the communication protocols of control systems (a process generally referred to as ''reverse engineering''), an

  13. The Relationship between Common Genetic Markers of Breast Cancer Risk and Chemotherapy-Induced Toxicity: A Case-Control Study

    Science.gov (United States)

    Kar, Siddhartha; Michailidou, Kyriaki; Hiller, Louise; Vallier, Anne-Laure; Ingle, Susan; Hardy, Richard; Bowden, Sarah J.; Dunn, Janet A.; Twelves, Chris; Poole, Christopher J.; Caldas, Carlos; Earl, Helena M.; Pharoah, Paul D. P.; Abraham, Jean E.

    2016-01-01

    Ninety-four common genetic variants are confirmed to be associated with breast cancer. This study tested the hypothesis that breast cancer susceptibility variants may also be associated with chemotherapy-induced toxicity through shared mechanistic pathways such as DNA damage response, an association that, to our knowledge, has not been previously investigated. The study included breast cancer patients who received neoadjuvant/adjuvant chemotherapy from the Pharmacogenetic SNPs (PGSNPS) study. For each patient, a breast cancer polygenic risk score was created from the 94 breast cancer risk variants, all of which were genotyped or successfully imputed in PGSNPS. Logistic regression was performed to test the association with two clinically important toxicities: taxane- related neuropathy (n = 1279) and chemotherapy-induced neutropenia (n = 1676). This study was well powered (≥96%) to detect associations between polygenic risk score and chemotherapy toxicity. Patients with high breast cancer risk scores experienced less neutropenia compared to those with low risk scores (adjusted p-value = 0.06). Exploratory functional pathway analysis was performed and no functional pathways driving this trend were identified. Polygenic risk was not associated with taxane neuropathy (adjusted p-value = 0.48). These results suggest that breast cancer patients with high genetic risk of breast cancer, conferred by common variants, can safely receive standard chemotherapy without increased risk of taxane-related sensory neuropathy or chemotherapy-induced neutropenia and may experience less neutropenia. As neutropenia has previously been associated with improved survival and may reflect drug efficacy, these patients may be less likely to benefit from standard chemotherapy treatment. PMID:27392074

  14. Genetics in psychiatry: common variant association studies

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2010-03-01

    Full Text Available Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.

  15. Association study of common genetic variants and HIV-1 acquisition in 6,300 infected cases and 7,200 controls.

    Directory of Open Access Journals (Sweden)

    Paul J McLaren

    Full Text Available Multiple genome-wide association studies (GWAS have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1. After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6 × 10⁻¹¹. However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception of CCR5Δ32 homozygosity. Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size.

  16. Common genetic risk variants of TLR2 are not associated with periodontitis in large European case-control populations

    NARCIS (Netherlands)

    Richter, G.M.; Graetz, C.; Pohler, P.; Nothnagel, M.; Dommisch, H.; Laine, M.L.; Folwaczny, M.; Noack, B.; Eickholz, P.; Groessner-Schreiber, B.; Jepsen, S.; Loos, B.G.; Schreiber, S.; Schaefer, A.S.

    2012-01-01

    Aim Involvement of TLR2 in the pathophysiology of periodontitis has widely been discussed, but hitherto, no validated genetic associations were reported. Previous association studies lacked sufficient statistical power and adequate haplotype information to draw unambiguous conclusions. The aim of

  17. Common genetic risk variants of TLR2 are not associated with periodontitis in large European case-control populations

    NARCIS (Netherlands)

    Richter, G.M.; Graetz, C.; Pohler, P.; Nothnagel, M.; Dommisch, H.; Laine, M.L.; Folwaczny, M.; Noack, B.; Eickholz, P.; Groessner-Schreiber, B.; Jepsen, S.; Loos, B.G.; Schreiber, S.; Schaefer, A.S.

    2012-01-01

    Aim Involvement of TLR2 in the pathophysiology of periodontitis has widely been discussed, but hitherto, no validated genetic associations were reported. Previous association studies lacked sufficient statistical power and adequate haplotype information to draw unambiguous conclusions. The aim of th

  18. Genetic diversity and population structure of common bean ...

    African Journals Online (AJOL)

    fire7-

    2016-12-28

    Dec 28, 2016 ... markers to assess the genetic diversity within and between common bean landraces, classifying them based on ... since the 1980's from continuous introduction of new ... control genotypes for the Andean and Mesoamerican gene pools, ... http://biology.anu.edu.au/GenAlEx/) was used to calculate genetic.

  19. Common Gene Variants Account for Most Genetic Risk for Autism

    Science.gov (United States)

    ... July 20, 2014 Common gene variants account for most genetic risk for autism Roles of heritability, mutations, ... factors. Population-Based Autism Genetics and Environment Study Most of the genetic risk for autism comes from ...

  20. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study

    DEFF Research Database (Denmark)

    Milne, Roger L; Gaudet, Mia M; Spurdle, Amanda B

    2010-01-01

    Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating...

  1. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study

    DEFF Research Database (Denmark)

    Milne, Roger L; Gaudet, Mia M; Spurdle, Amanda B

    2010-01-01

    Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in th...

  2. Genetic control of the fungus Colletotrichum lindemuthianum (Sacc. & Magn. Scrib. reaction and corona color in the common bean (Phaseolus vulgaris L.

    Directory of Open Access Journals (Sweden)

    H.A. de Mendonça

    1998-09-01

    Full Text Available An important trait for common bean (Phaseolus vulgaris L. cultivars with Carioca type grain is resistance to Colletotrichum lindemuthianum, which causes anthracnose and a pale corona. The present study was conducted to understand the genetic control of common bean reaction to the fungus and of the corona color, to provide guides to future breeding studies. Genotypes P-45, with brown corona, and EMGOPA 201-Ouro, with yellow corona, are resistant to C. lindemuthianum. Cultivar Carioca is susceptible to anthracnose, but it has desirable grain and corona color. Anthracnose resistance and corona color were studied in the F1 and F2 generations of three populations resulting from crosses of P-45, EMGOPA 201-Ouro, and Carioca. The Carioca x P-45 cross indicated that the Mex.2 allele, which conditions resistance to the pathogen, is linked with a recombination frequency of 0.0604 ± 0.0232 to one of the alleles which determines the dark brown corona color. The EMGOPA 201-Ouro x Carioca cross revealed that the resistance allele of EMGOPA 201-Ouro was independent from the alleles which determine the yellow corona. These resistance alleles were also determined to be independent according to EMGOPA 201-Ouro x P-45 cross results.As cultivares de feijão com grão tipo Carioca devem possuir, entre outros caracteres, resistência ao Colletotrichum lindemuthianum, agente causal da antracnose, e possuir halo de cor clara. Assim, o objetivo do presente estudo foi conhecer o controle genético desses dois caracteres, visando orientar os futuros trabalhos de melhoramento. Os genitores utilizados foram P-45, EMGOPA 201-Ouro e Carioca-300V, sendo que o P-45 possui halo marrom escuro e o EMGOPA 201-Ouro, halo amarelo, ambos resistentes ao Colletotrichum lindemuthianum. O genitor Carioca-300V é suscetível, porém possui cor de grão e de halo desejáveis. Do intercruzamento desses genitores obtiveram-se três populações que foram avaliadas nas gerações F1 e F2 para

  3. Hybridization effects and genetic diversity of the common and black-tufted marmoset (Callithrix jacchus and Callithrix penicillata) mitochondrial control region.

    Science.gov (United States)

    Malukiewicz, Joanna; Boere, Vanner; Fuzessy, Lisieux F; Grativol, Adriana D; French, Jeffrey A; de Oliveira e Silva, Ita; Pereira, Luiz C M; Ruiz-Miranda, Carlos R; Valença, Yuri M; Stone, Anne C

    2014-12-01

    Hybridization is continually documented in primates, but effects of natural and anthropogenic hybridization on biodiversity are still unclear and differentiating between these contexts remains challenging in regards to primate evolution and conservation. Here, we examine hybridization effects on the mitochondrial DNA (mtDNA) control region of Callithrix marmosets, which provide a unique glimpse into interspecific mating under distinct anthropogenic and natural conditions. DNA was sampled from 40 marmosets along a 50-km transect from a previously uncharacterized hybrid zone in NE Brazil between the ranges of Callithrix jacchus and Callithrix penicillata. DNA was also collected from 46 marmosets along a 30-km transect in a hybrid zone in Rio de Janeiro state, Brazil, where exotic marmosets appeared in the 1980s. Combining Callithrix DNA sampled inside and outside of these hybrid zones, phylogenetic and network analyses show C. jacchus and C. penicillata being parental species to sampled hybrids. We expand limited Callithrix population genetics work by describing mtDNA diversity and demographic history of these parental species. We show ancient population expansion in C. jacchus and historically constant population size in C. penicillata, with the latter being more genetically diverse than the former. The natural hybrid zone contained higher genetic diversity relative to the anthropogenic zone. While our data suggest hybrid swarm formation within the anthropogenic zone due to removed physical reproductive barriers, this pattern is not seen in the natural hybrid zone. These results suggest different genetic dynamics within natural and anthropogenic hybridization contexts that carry important implications for primate evolution and conservation.

  4. Identifying genetics and genomics nursing competencies common among published recommendations.

    Science.gov (United States)

    Greco, Karen E; Salveson, Catherine

    2009-10-01

    The purpose of this article is to identify published recommendations for genetics and genomics competencies or curriculum for nurses in the United States and to summarize genetic and genomic nursing competencies based on common themes among these documents. A review of the literature between January 1998 and June 2008 was conducted. Efforts were also made to access the gray literature. Five consensus documents describing recommendations for genetics and genomics competencies for nurses meeting inclusion criteria were analyzed. Twelve genetics and genomics competencies were created based on common themes among the recommendations. These competencies include: demonstrate an understanding of basic genetic and genomic concepts, provide and explain genetic and genomic information, refer to appropriate genetics professionals and services, and identify the limits of one's own genetics and genomics expertise. The competencies represent fundamental genetics and genomics competencies for nurses on the basis of common themes among several consensus recommendations identified in the literature.

  5. Nutrition and genetic susceptibility to common diseases.

    Science.gov (United States)

    Motulsky, A G

    1992-06-01

    Genetic factors play a role in chronic disease and conditions such as coronary heart disease, hypertension, and obesity. Individual responses to nutritional factors involved in such conditions vary depending upon a person's genetic make-up. The role of individual genes is best understood for the hyperlipidemias that predispose to coronary heart disease. Until more and better information on gene-nutritional interactions is available, general population-wide recommendations regarding a prudent diet appear reasonable. At the same time, high risk screening for certain conditions such as the hyperlipidemias is appropriate.

  6. Malheur - Common Carp Movement Control

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Invasive common carp Cyprinus carpio were introduced into the Harney Basin in the 1920’s and were recognized as a problem in Malheur Lake in 1952. The common carp...

  7. Genetics Home Reference: common variable immune deficiency

    Science.gov (United States)

    ... or Free article on PubMed Central Park JH, Resnick ES, Cunningham-Rundles C. Perspectives on common variable ... on PubMed or Free article on PubMed Central Resnick ES, Cunningham-Rundles C. The many faces of ...

  8. Hand controller commonality evaluation process

    Science.gov (United States)

    Stuart, Mark A.; Bierschwale, John M.; Wilmington, Robert P.; Adam, Susan C.; Diaz, Manuel F.; Jensen, Dean G.

    1993-01-01

    Hand controller selection for NASA's Orbiter and Space Station Freedom is an important area of human-telerobot interface design and evaluation. These input devices will control remotely operated systems that include large crane-like manipulators (e.g., Remote Manipulator System or RMS), smaller, more dexterous manipulators (e.g., Flight Telerobotic Servicer or FTS), and free flyers (e.g., Orbital Maneuvering Vehicle or OMV). Candidate hand controller configurations for these systems vary in many ways: shape, size, number of degrees-of-freedom (DOF), operating modes, provision of force reflection, range of movement, and 'naturalness' of use. Unresolved design implementation issues remain, including such topics as how the current Orbiter RMS rotational and translational rate hand controllers compare with the proposed Space Station Freedom hand controllers, the advantages that position hand controllers offer for these applications, and whether separate hand controller configurations are required for each application. Since previous studies contain little empirical hand controller task performance data, a controlled study is needed that tests Space Station Freedom candidate hand controllers during representative tasks. This study also needs to include anthropometric and biomechanical considerations.

  9. Superoxide-dismutase deficient mutants in common beans (Phaseolus vulgaris L.): genetic control, differential expressions of isozymes, and sensitivity to arsenic.

    Science.gov (United States)

    Talukdar, Dibyendu; Talukdar, Tulika

    2013-01-01

    Two common bean (Phaseolus vulgaris L.) mutants, sodPv 1 and sodPv 2, exhibiting foliar superoxide dismutase (SOD) activity of only 25% and 40% of their mother control (MC) cv. VL 63 were isolated in EMS-mutagenized (0.15%, 8 h) M2 progeny. Native-PAGE analysis revealed occurrence of Mn SOD, Fe SOD, Cu/Zn SOD I and Cu/Zn SOD II isozymes in MC, while Fe SOD, and Mn SOD were not formed in sodPv 1 and sodPv 2 leaves, respectively. In-gel activity of individual isozymes differed significantly among the parents. SOD deficiency is inherited as recessive mutations, controlled by two different nonallelic loci. Gene expressions using qRT PCR confirmed higher expressions of Cu/Zn SOD transcripts in both mutants and the absence of Fe SOD in sodPv 1 and Mn SOD in sodPv 2. In 50 μM arsenic, Cu/Zn SODs genes were further upregulated but other isoforms downregulated in the two mutants, maintaining SOD activity in its control level. In an F2 double mutants of sodPv 1 × sodPv 2, no Fe SOD, and Mn SOD expressions were detectable, while both Cu/Zn SODs are down-regulated and arsenic-induced leaf necrosis appeared. In contrast to both mutants, ROS-imaging study revealed overaccumulation of both superoxides and H2O2 in leaves of double mutant.

  10. Superoxide-Dismutase Deficient Mutants in Common Beans (Phaseolus vulgaris L.: Genetic Control, Differential Expressions of Isozymes, and Sensitivity to Arsenic

    Directory of Open Access Journals (Sweden)

    Dibyendu Talukdar

    2013-01-01

    Full Text Available Two common bean (Phaseolus vulgaris L. mutants, sodPv 1 and sodPv 2, exhibiting foliar superoxide dismutase (SOD activity of only 25% and 40% of their mother control (MC cv. VL 63 were isolated in EMS-mutagenized (0.15%, 8 h M2 progeny. Native-PAGE analysis revealed occurrence of Mn SOD, Fe SOD, Cu/Zn SOD I and Cu/Zn SOD II isozymes in MC, while Fe SOD, and Mn SOD were not formed in sodPv 1 and sodPv 2 leaves, respectively. In-gel activity of individual isozymes differed significantly among the parents. SOD deficiency is inherited as recessive mutations, controlled by two different nonallelic loci. Gene expressions using qRT PCR confirmed higher expressions of Cu/Zn SOD transcripts in both mutants and the absence of Fe SOD in sodPv 1 and Mn SOD in sodPv 2. In 50 M arsenic, Cu/Zn SODs genes were further upregulated but other isoforms downregulated in the two mutants, maintaining SOD activity in its control level. In an F2 double mutants of sodPv 1 × sodPv 2, no Fe SOD, and Mn SOD expressions were detectable, while both Cu/Zn SODs are down-regulated and arsenic-induced leaf necrosis appeared. In contrast to both mutants, ROS-imaging study revealed overaccumulation of both superoxides and H2O2 in leaves of double mutant.

  11. 49 CFR 1185.5 - Common control.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 8 2010-10-01 2010-10-01 false Common control. 1185.5 Section 1185.5... OF TRANSPORTATION RULES OF PRACTICE INTERLOCKING OFFICERS § 1185.5 Common control. It shall not be... carriers if such carriers are operated under common control or management either: (a) Pursuant to...

  12. Evolution of a Common Controller

    Science.gov (United States)

    2012-04-01

    focused on distribution but with the same design concepts used in MOCU. Remote Operator Control Services (ROCS) will use an HTML5 enabled browser to...provide the presentation layer. HTML5 and WebGL provide most of the capability provided within MOCU 3 but in a standardized format. Data is

  13. Genetics of Common Endocrine Disease: The Present and the Future.

    Science.gov (United States)

    Goodarzi, Mark O

    2016-03-01

    In honor of the 75th issue of the Journal of Clinical Endocrinology and Metabolism, the author was invited to present his perspectives on genetics in human endocrinology. This paper reviews what the field has achieved in the genetics of common endocrine disease, and offers predictions on where the field will move in the future and its impact on endocrine clinical practice. The October 2015 data release of the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) Catalog of Published Genome-wide Association Studies was queried regarding endocrinologic diseases and traits. PubMed searches were focused on genetic prediction of disease, genetic findings and drug targets, functional interrogation of genetic loci, use of genetics to subtype disease, missing heritability, systems genomics, and higher order chromatin structures as regulators of gene function. Nearly a quarter of genome wide association study findings concern endocrinologic diseases and traits. While these findings have not yet dramatically altered clinical care, genetics will have a major impact by providing the drug targets of tomorrow, facilitated by experimental and bioinformatic advances that will shorten the time from gene discovery to drug development. Use of genetic findings to subtype common endocrine disease will allow more precise prevention and treatment efforts. Future advances will allow us to move away from the common view of DNA as a string of letters, allowing exploration of higher order structure that likely explains much "missing heritability." The future will see a greater role of genetics at the bedside, with genetic epidemiologic discoveries leading not only to new treatments of endocrine disease, but also helping us prescribe the right drug to the right patients by allowing subclassification of common heterogeneous endocrine conditions. Future technological breakthroughs will reveal the heritable mysteries hidden in chromatin structure, leading to a

  14. Common genetic variants influence human subcortical brain structures

    OpenAIRE

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro,; Desrivieres, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume de...

  15. 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.

  16. Worldwide genetic differentiation in the common fouling barnacle, Amphibalanus amphitrite

    KAUST Repository

    Chen, Hsi-Nien

    2014-10-21

    © 2014, © 2014 Taylor & Francis. Amphibalanus amphitrite is a common fouling barnacle distributed globally in tropical and subtropical waters. In the present study, the genetic (mitochondrial cytochrome oxidase subunit I) and morphological differentiation in A. amphitrite from 25 localities around the world were investigated. The results revealed three clades within A. amphitrite with a genetic divergence of ~ 4% among clades, whereas there were no diagnostic morphological differences among clades. Clade 1 is widely distributed in both temperate and tropical waters, whereas Clade 3 is currently restricted to the tropical region. The deep divergence among clades suggests historical isolation within A. amphitrite; thus, the present geographical overlaps are possibly a result of the combined effects of rising sea level and human-mediated dispersals. This study highlights the genetic differentiation that exists in a common, widely distributed fouling organism with great dispersal potential; future antifouling research should take into account the choice of lineages.

  17. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    Hibar, D.P.; Stein, J.L.; Renteria, M.E.; Arias Vasquez, A.; Desrivieres, S.; Jahanshad, N.; Toro, R.; Wittfeld, K.; Abramovic, L.; Andersson, M.; Aribisala, B.S.; Armstrong, N.J.; Bernard, M.; Bohlken, M.M.; Boks, M.P.; Bralten, J.; Brown, A.A.; Chakravarty, M.M.; Chen, Q.; Ching, C.R.; Cuellar-Partida, G.; Braber, A.; Giddaluru, S.; Goldman, A.L.; Grimm, O.; Guadalupe, T.; Hass, J.; Woldehawariat, G.; Holmes, A.J.; Hoogman, M.; Janowitz, D.; Jia, T.; Kim, S.; Klein, M.; Kraemer, B.; Lee, P.H.; Olde Loohuis, L.M.; Luciano, M.; Macare, C.; Mather, K.A.; Mattheisen, M.; Milaneschi, Y.; Nho, K.; Papmeyer, M.; Ramasamy, A.; Risacher, S.L.; Roiz-Santianez, R.; Rose, E.J.; Salami, A.; Samann, P.G.; Schmaal, L.; Schork, A.J.; Shin, J.; Strike, L.T.; Teumer, A.; Donkelaar, M.M.J. van; Eijk, K.R. van; Walters, R.K.; Westlye, L.T.; Whelan, C.D.; Winkler, A.M.; Zwiers, M.P.; Alhusaini, S.; Athanasiu, L.; Ehrlich, S.; Hakobjan, M.M.; Hartberg, C.B.; Haukvik, U.K.; Heister, A.J.; Hoehn, D.; Kasperaviciute, D.; Liewald, D.C.; Lopez, L.M.; Makkinje, R.R.; Matarin, M.; Naber, M.; McKay, D.R.; Needham, M.; Nugent, A.C.; Putz, B.; Royle, N.A.; Shen, L.; Sprooten, E.; Trabzuni, D.; Marel, S.S. van der; Hulzen, K.J.E. van; Walton, E.; Wolf, C.; Almasy, L.; Ames, D.; Arepalli, S.; Assareh, A.A.; Bastin, M.E.; Brodaty, H.; Bulayeva, K.B.; Carless, M.A.; Cichon, S.; Corvin, A.; Curran, J.E.; Czisch, M.; Fisher, S.E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common

  18. The genetic diversity and population structure of common bean ...

    African Journals Online (AJOL)

    SAM

    2014-07-16

    Jul 16, 2014 ... variation and, hence, restricting the amount of adapted genetic diversity ... the phenotypic diversity of common bean in Uganda. The selection ... The place of collection/origin was also consi- dered in ..... Bean Research and Development Programs at NaCRRI and CIAT .... Evolution 92:1101-1104. Kami JA ...

  19. Evidence of Common Genetic Overlap Between Schizophrenia and Cognition.

    Science.gov (United States)

    Hubbard, Leon; Tansey, Katherine E; Rai, Dheeraj; Jones, Peter; Ripke, Stephan; Chambert, Kimberly D; Moran, Jennifer L; McCarroll, Steven A; Linden, David E J; Owen, Michael J; O'Donovan, Michael C; Walters, James T R; Zammit, Stanley

    2016-05-01

    Cognitive impairment is a core feature of schizophrenia but there is limited understanding of the genetic relationship between cognition in the general population and schizophrenia. We examine how common variants associated with schizophreniaen massecontribute to childhood cognitive ability in a population-based sample, and the extent to which common genetic variants associated with childhood cognition explain variation in schizophrenia. Schizophrenia polygenic risk scores were derived from the Psychiatric Genomics Consortium (n= 69 516) and tested for association with IQ, attention, processing speed, working memory, problem solving, and social cognition in over 5000 children aged 8 from the Avon Longitudinal Study of Parents and Children birth cohort. Polygenic scores for these cognitive domains were tested for association with schizophrenia in a large UK schizophrenia sample (n= 11 853). Bivariate genome-wide complex trait analysis (GCTA) estimated the amount of shared genetic factors between schizophrenia and cognitive domains. Schizophrenia polygenic risk score was associated with lower performance IQ (P= .001) and lower full IQ (P= .013). Polygenic score for performance IQ was associated with increased risk for schizophrenia (P= 3.56E-04). Bivariate GCTA revealed moderate genetic correlation between schizophrenia and both performance IQ (rG= -.379,P= 6.62E-05) and full IQ (rG= -.202,P= 5.00E-03), with approximately 14% of the genetic component of schizophrenia shared with that for performance IQ. Our results support the presence of shared common genetic factors between schizophrenia and childhood cognitive ability. We observe a genetic relationship between schizophrenia and performance IQ but not verbal IQ or other cognitive variables, which may have implications for studies utilizing cognitive endophenotypes for psychosis.

  20. Is there a Common Genetic Basis for Autoimmune Diseases?

    Directory of Open Access Journals (Sweden)

    Juan-Manuel Anaya

    2006-01-01

    Full Text Available Autoimmune diseases (ADs represent a diverse collection of diseases in terms of their demographic profile and primary clinical manifestations. The commonality between them however, is the damage to tissues and organs that arises from the response to self-antigens. The presence of shared pathophysiological mechanisms within ADs has stimulated searches for common genetic roots to these diseases. Two approaches have been undertaken to sustain the “common genetic origin” theory of ADs. Firstly, a clinical genetic analysis showed that autoimmunity aggregates within families of probands diagnosed with primary Sjögren's (pSS syndrome or type 1 diabetes mellitus (T1D. A literature review supported the establishment of a familiar cluster of ADs depending upon the proband's disease phenotype. Secondly, in a same and well-defined population, a large genetic association study indicated that a number of polymorphic genes (i.e. HLA-DRB1, TNF and PTPN22 influence the susceptibility for acquiring different ADs. Likewise, association and linkage studies in different populations have revealed that several susceptibility loci overlap in ADs, and clinical studies have shown that frequent clustering of several ADs occurs. Thus, the genetic factors for ADs consist of two types: those which are common to many ADs (acting in epistatic pleitropy and those that are specific to a given disorder. Their identification and functional characterization will allow us to predict their effect as well as to indicate potential new therapeutic interventions. Both autoimmunity family history and the co-occurrence of ADs in affected probands should be considered when performing genetic association and linkage studies.

  1. Analysis of mutants from a genetic screening reveals the control of intestine and liver development by many common genes in zebrafish.

    Science.gov (United States)

    Jiang, Faming; Chen, Jiehui; Ma, Xirui; Huang, Chao; Zhu, Shicheng; Wang, Fei; Li, Li; Luo, Lingfei; Ruan, Hua; Huang, Honghui

    2015-05-01

    Both the intestine and liver develop from the endoderm, yet little is known how these two digestive organs share and differ in their developmental programs, at the molecular level. A classical forward genetic screen, with no gene bias, is an effective way to address this question by examining the defects of the intestine and liver in obtained mutants to assess mutated genes responsible for the development of either organ or both. We report here such a screen in zebrafish. ENU was used as the mutagen because of its high mutagenic efficiency and no site preference. Embryos were collected at 3.5 dpf for RNA whole mount in situ hybridization with a cocktail probe of the intestine marker ifabp and the liver marker lfabp to check phenotypes and determine their parental heterozygosis. A total of 52 F2 putative mutants were identified, and those with general developmental defects were aborted. To rule out non-inheritable phenotypes caused by high mutation background, F2 putative mutants were outcrossed with wild type fish and a re-screen in F3 generations was performed. After complementation tests between F3 mutants with similar phenotypes originating from the same F2 families, a total of 37 F3 mutant lines originated from 22 F2 families were identified after screening 78 mutagenized genomes. Classification of mutant phenotypes indicated that 31 out of the 37 mutants showed defects in both the intestine and liver. In addition, four "intestine specific mutants" and two "liver specific mutants" showed selectively more severe phenotype in the intestine and liver respectively. These results suggested that the intestine and liver share a substantial number of essential genes during both organs development in zebrafish. Further studies of the mutants are likely to shed more insights into the molecular basis of the digestive system development in the zebrafish and vertebrate.

  2. Genetic diversity analysis of common beans based on molecular markers.

    Science.gov (United States)

    Gill-Langarica, Homar R; Muruaga-Martínez, José S; Vargas-Vázquez, M L Patricia; Rosales-Serna, Rigoberto; Mayek-Pérez, Netzahualcoyotl

    2011-10-01

    A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5% polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  3. Genetic diversity analysis of common beans based on molecular markers

    Directory of Open Access Journals (Sweden)

    Homar R. Gill-Langarica

    2011-01-01

    Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  4. Genetic diversity analysis of common beans based on molecular markers

    Science.gov (United States)

    Gill-Langarica, Homar R.; Muruaga-Martínez, José S.; Vargas-Vázquez, M.L. Patricia; Rosales-Serna, Rigoberto; Mayek-Pérez, Netzahualcoyotl

    2011-01-01

    A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5% polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation. PMID:22215964

  5. Genetic diversity analysis of common beans based on molecular markers

    Directory of Open Access Journals (Sweden)

    Homar R. Gill-Langarica

    Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  6. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study.

    Science.gov (United States)

    Milne, Roger L; Gaudet, Mia M; Spurdle, Amanda B; Fasching, Peter A; Couch, Fergus J; Benítez, Javier; Arias Pérez, José Ignacio; Zamora, M Pilar; Malats, Núria; Dos Santos Silva, Isabel; Gibson, Lorna J; Fletcher, Olivia; Johnson, Nichola; Anton-Culver, Hoda; Ziogas, Argyrios; Figueroa, Jonine; Brinton, Louise; Sherman, Mark E; Lissowska, Jolanta; Hopper, John L; Dite, Gillian S; Apicella, Carmel; Southey, Melissa C; Sigurdson, Alice J; Linet, Martha S; Schonfeld, Sara J; Freedman, D Michal; Mannermaa, Arto; Kosma, Veli-Matti; Kataja, Vesa; Auvinen, Päivi; Andrulis, Irene L; Glendon, Gord; Knight, Julia A; Weerasooriya, Nayana; Cox, Angela; Reed, Malcolm Wr; Cross, Simon S; Dunning, Alison M; Ahmed, Shahana; Shah, Mitul; Brauch, Hiltrud; Ko, Yon-Dschun; Brüning, Thomas; Lambrechts, Diether; Reumers, Joke; Smeets, Ann; Wang-Gohrke, Shan; Hall, Per; Czene, Kamila; Liu, Jianjun; Irwanto, Astrid K; Chenevix-Trench, Georgia; Holland, Helene; Giles, Graham G; Baglietto, Laura; Severi, Gianluca; Bojensen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; John, Esther M; West, Dee W; Whittemore, Alice S; Vachon, Celine; Olson, Janet E; Fredericksen, Zachary; Kosel, Matthew; Hein, Rebecca; Vrieling, Alina; Flesch-Janys, Dieter; Heinz, Judith; Beckmann, Matthias W; Heusinger, Katharina; Ekici, Arif B; Haeberle, Lothar; Humphreys, Manjeet K; Morrison, Jonathan; Easton, Doug F; Pharoah, Paul D; García-Closas, Montserrat; Goode, Ellen L; Chang-Claude, Jenny

    2010-01-01

    Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified.

  7. The Association between Pediatric NAFLD and Common Genetic Variants

    Directory of Open Access Journals (Sweden)

    Giuseppina Rosaria Umano

    2017-06-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is one of the most common complications of obesity. Several studies have shown that genetic predisposition probably plays an important role in its pathogenesis. In fact, in the last few years a large number of genetic studies have provided compelling evidence that some gene variants, especially those in genes encoding proteins regulating lipid metabolism, are associated with intra-hepatic fat accumulation. Here we provide a comprehensive review of the gene variants that have affected the natural history of the disease.

  8. 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

  9. Assessment of genetic associations between common single nucleotide polymorphisms in RIG-I-like receptor and IL-4 signaling genes and severe respiratory syncytial virus infection in children: a candidate gene case-control study.

    Directory of Open Access Journals (Sweden)

    Nico Marr

    Full Text Available The majority of cases of severe pediatric respiratory syncytial virus (RSV infection occur in otherwise healthy infants who have no identifiable risk factors, suggesting that additional subclinical factors, such as population genetic variation, influence the course of RSV infection. The objective of this study was to test if common single nucleotide polymorphisms (SNPs in genes encoding for immune signalling components of the RIG-I-like receptor (RLR and IL-4-signalling pathways affect the outcome of RSV infection in early life. We genotyped 8 SNPs using allele-specific probes combined with real-time PCR. Each of the SNPs tested had previously been established to have a functional impact on immune responsiveness and two of the SNPs in the IL4 and IL4R genes had previously been associated with severe RSV bronchiolitis. Association with susceptibility to severe RSV infection was tested by statistically comparing genotype and allele frequencies in infants and young children hospitalized with severe RSV bronchiolitis (n = 140 with two control groups-children who tested positive for RSV but did not require hospitalization (n = 100, and a general population control group (n = 285. Our study was designed with sufficient power (>80% to detect clinically-relevant associations with effect sizes ≥1.5. However, we detected no statistically significant differences in allele and genotype frequencies of the investigated SNPs between the inpatient and control groups. To conclude, we could not replicate the previously reported association with SNPs in the IL4 and IL4R genes in our independent cohort, nor did we find that common SNPs in genes encoding for RLRs and the downstream adapter MAVS were associated with susceptibility to severe RSV infections. Despite the existing evidence demonstrating a functional immunological impact of these SNPs, our data suggest that the biological effect of each individual SNP is unlikely to affect clinical outcomes

  10. Genetic Correlation between Body Fat Percentage and Cardiorespiratory Fitness Suggests Common Genetic Etiology

    DEFF Research Database (Denmark)

    Schnurr, Theresia Maria; Gjesing, Anette Marianne Prior; Sandholt, Camilla Helene

    2016-01-01

    Objectives: It has long been discussed whether fitness or fatness is a more important determinant of health status. If the same genetic factors that promote body fat percentage (body fat%) are related to cardiorespiratory fitness (CRF), part of the concurrent associations with health outcomes could...... reflect a common genetic origin. In this study we aimed to 1) examine genetic correlations between body fat% and CRF; 2) determine whether CRF can be attributed to a genetic risk score (GRS) based on known body fat% increasing loci; and 3) examine whether the fat mass and obesity associated (FTO) locus...... associates with CRF. Methods: Genetic correlations based on pedigree information were examined in a family based cohort (n = 230 from 55 families). For the genetic association analyses, we examined two Danish population-based cohorts (ntotal = 3206). The body fat% GRS was created by summing the alleles...

  11. Genetic Correlation between Body Fat Percentage and Cardiorespiratory Fitness Suggests Common Genetic Etiology

    DEFF Research Database (Denmark)

    Schnurr, Theresia M; Gjesing, Anette P; Sandholt, Camilla H

    2016-01-01

    OBJECTIVES: It has long been discussed whether fitness or fatness is a more important determinant of health status. If the same genetic factors that promote body fat percentage (body fat%) are related to cardiorespiratory fitness (CRF), part of the concurrent associations with health outcomes could...... reflect a common genetic origin. In this study we aimed to 1) examine genetic correlations between body fat% and CRF; 2) determine whether CRF can be attributed to a genetic risk score (GRS) based on known body fat% increasing loci; and 3) examine whether the fat mass and obesity associated (FTO) locus...... associates with CRF. METHODS: Genetic correlations based on pedigree information were examined in a family based cohort (n = 230 from 55 families). For the genetic association analyses, we examined two Danish population-based cohorts (ntotal = 3206). The body fat% GRS was created by summing the alleles...

  12. Common genetic variants influence human subcortical brain structures.

    Science.gov (United States)

    Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy

    2015-04-01

    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

  13. Common genetic variants influence human subcortical brain structures

    Science.gov (United States)

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

  14. New IBD genetics: common pathways with other diseases.

    Science.gov (United States)

    Lees, C W; Barrett, J C; Parkes, M; Satsangi, J

    2011-12-01

    Complex disease genetics has been revolutionised in recent years by the advent of genome-wide association (GWA) studies. The chronic inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis have seen notable successes culminating in the discovery of 99 published susceptibility loci/genes (71 Crohn's disease; 47 ulcerative colitis) to date. Approximately one-third of loci described confer susceptibility to both Crohn's disease and ulcerative colitis. Amongst these are multiple genes involved in IL23/Th17 signalling (IL23R, IL12B, JAK2, TYK2 and STAT3), IL10, IL1R2, REL, CARD9, NKX2.3, ICOSLG, PRDM1, SMAD3 and ORMDL3. The evolving genetic architecture of IBD has furthered our understanding of disease pathogenesis. For Crohn's disease, defective processing of intracellular bacteria has become a central theme, following gene discoveries in autophagy and innate immunity (associations with NOD2, IRGM, ATG16L1 are specific to Crohn's disease). Genetic evidence has also demonstrated the importance of barrier function to the development of ulcerative colitis (HNF4A, LAMB1, CDH1 and GNA12). However, when the data are analysed in more detail, deeper themes emerge including the shared susceptibility seen with other diseases. Many immune-mediated diseases overlap in this respect, paralleling the reported epidemiological evidence. However, in several cases the reported shared susceptibility appears at odds with the clinical picture. Examples include both type 1 and type 2 diabetes mellitus. In this review we will detail the presently available data on the genetic overlap between IBD and other diseases. The discussion will be informed by the epidemiological data in the published literature and the implications for pathogenesis and therapy will be outlined. This arena will move forwards very quickly in the next few years. Ultimately, we anticipate that these genetic insights will transform the landscape of common complex diseases such as IBD.

  15. The role of common genetic variants in atrial fibrillation

    DEFF Research Database (Denmark)

    Paludan-Muller, Christian; Svendsen, Jesper H.; Olesen, Morten S.

    2016-01-01

    this approach. Highly penetrant variants in lone AF have also been described in a number of cases. Furthermore, familial AF, although rare, have been recognized for many years. Variants associated with AF have been identified in more than 40 genes, including cardiac gap junction proteins, ion channels and beta......This review focuses on the genetic basis of atrial fibrillation (AF) and the role of variants in the susceptibility of developing the disease. AF is the most common cardiac arrhythmia affecting 1-2% of the general population. Studies in the last decade have demonstrated that AF, and in particular...... and non-cardiac diseases....

  16. Common Genetic Variants Found in HLA and KIR Immune Genes in Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Anthony R Torres

    2016-10-01

    Full Text Available The common variant - common disease hypothesis was proposed to explain diseases with strong inheritance. This model suggests that a genetic disease is the result of the combination of several common genetic variants. Common genetic variants are described as a 5% frequency differential between diseased versus matched control populations. This theory was recently supported by an epidemiology paper stating that about 50% of genetic risk for autism resides in common variants. However, rare variants, rather than common variants, have been found in numerous genome wide genetic studies and many have concluded that the common variant—common disease hypothesis is incorrect. One interpretation is that rare variants are major contributors to genetic diseases and autism involves the interaction of many rare variants, especially in the brain. It is obvious there is much yet to be learned about autism genetics.Evidence has been mounting over the years indicating immune involvement in autism, particularly the HLA genes on chromosome 6 and KIR genes on chromosome 19. These two large multigene complexes have important immune functions and have been shown to interact to eliminate unwanted virally infected and malignant cells. HLA proteins have important functions in antigen presentation in adaptive immunity and specific epitopes on HLA class I proteins act as cognate ligands for KIR receptors in innate immunity. Data suggests that HLA alleles and KIR activating genes/haplotypes are common variants in different autism populations. For example, class I allele (HLA-A2 and HLA-G 14bp-indel frequencies are significantly increased by more than 5% over control populations (Table2. The HLA-DR4 Class II and shared epitope frequencies are significantly above the control populations (Table 2. Three activating KIR genes: 3DS1, 2DS1 and 2DS2 have increased frequencies of 15%, 22% and 14% in autism populations, respectively. There is a 6% increase in total activating KIR

  17. Italian Common Bean Landraces: History, Genetic Diversity and Seed Quality

    Directory of Open Access Journals (Sweden)

    Angela R. Piergiovanni

    2010-05-01

    Full Text Available The long tradition of common bean cultivation in Italy has allowed the evolution of many landraces adapted to restricted areas. Nowadays, in response to market demands, old landraces are gradually being replaced by improved cultivars. However, landraces still survive in marginal areas of several Italian regions. Most of them appear severely endangered with risk of extinction due to the advanced age of the farmers and the socio-cultural context where they are cultivated. The present contribution is an overview of the state of the art about the knowledge of Italian common bean germplasm, describing the most important and recent progresses made in its characterization, including genetic diversity and nutritional aspects.

  18. Controle genético da qualidade da vagem em cruzamento de feijão-vagem e feijão-comum Genetic control of pod quality in a cross between snap beans and common bean

    Directory of Open Access Journals (Sweden)

    Keny Henrique Mariguele

    2008-01-01

    Full Text Available O objetivo deste trabalho foi determinar os tipos principais de ações gênicas responsáveis pela expressão fenotípica de alguns caracteres de qualidade da vagem, em cruzamento de feijão-vagem e feijão-comum. Foram avaliadas duas populações segregantes (F2 e F2:3, além das linhagens parentais. Como genitora feminina, utilizou-se a cultivar de feijão-vagem Conquista Rasteiro e, como genitora masculina, a linhagem de feijão-comum H126. Foram avaliados: comprimento da vagem, largura entre as suturas, largura das valvas, formato da vagem e teor de fibra da vagem . Os efeitos não-aditivos destacaram-se em todas as características avaliadas. Embora tenha ocorrido predominância dos efeitos genéticos sobre os ambientais, nas características comprimento e formato da vagem e teor de fibra, a eficiência da seleção em plantas individuais tendeu a ser bastante baixa nas gerações segregantes pouco avançadas, em razão dos baixos valores da herdabilidade no sentido restrito, exceto para formato da vagem. O predomínio dos efeitos genéticos sobre os ambientais em todas as características em nível de família, associado a valores de herdabilidade no sentido restrito em famílias F2:3, indica a alta eficiência para a seleção de famílias nas gerações segregantes pouco avançadas, com relação a todas as características, exceto para comprimento e teor de fibra.The objective of this work was to study the main gene actions involved in phenotypic expression of pod quality in a cross between snap beans and common bean. Two segregating populations (F2 and F2:3 and the parental lines were evaluated. The snap bean cultivar Conquista Rasteiro was used as the female parent, and the common bean line H126 as the male parent. Pod length, between-suture width, valve width, pod shape, and percentage of pod fiber were evaluated. Non-additive gene effects were important for all traits evaluated. Even though genetic effects were higher than the

  19. Genetic Control of Potassium Channels.

    Science.gov (United States)

    Amin, Ahmad S; Wilde, Arthur A M

    2016-06-01

    Approximately 80 genes in the human genome code for pore-forming subunits of potassium (K(+)) channels. Rare variants (mutations) in K(+) channel-encoding genes may cause heritable arrhythmia syndromes. Not all rare variants in K(+) channel-encoding genes are necessarily disease-causing mutations. Common variants in K(+) channel-encoding genes are increasingly recognized as modifiers of phenotype in heritable arrhythmia syndromes and in the general population. Although difficult, distinguishing pathogenic variants from benign variants is of utmost importance to avoid false designations of genetic variants as disease-causing mutations.

  20. Genetic basis of common diseases: the general theory of Mendelian recessive genetics.

    Science.gov (United States)

    Hutchinson, Michael; Spanaki, Cleanthe; Lebedev, Sergey; Plaitakis, Andreas

    2005-01-01

    Common diseases tend to appear sporadically, i.e., they appear in an individual who has no first or second degree relatives with the disease. Yet diseases are often associated with a slight but definite increase in risk to the children of an affected individual. This weak pattern of inheritability cannot be explained by conventional interpretations of Mendelian genetics, and it is therefore commonly held that there is "incomplete penetrance" of a gene, or that there are polygenic, or multifactorial modes of inheritance. However, such arguments are heuristic and lack predictive power. Here, we explore the possibility that "incomplete penetrance" means the existence of a second, disease-related, gene. By examining in detail a specific common condition, Parkinson's disease (PD), we show that the sporadic form of the disease can be fully explained by a compact fully penetrant genotype involving an interaction between two, and only two, genes. In this model, therefore PD is fundamentally genetic. Our digenic model is complementary to Mendelian recessive genetics, but taken together with the latter forms a complete description for recessive genetics on one chromosome. It explains the slight increase in risk to the children if one parent has sporadic PD, and makes strict predictions where both parents coincidentally have sporadic PD. These predictions were verified in two large and carefully selected kindred, where the data also argue against other genetic models, including oligogenic and polygenic schemes. Since the inheritance patterns of sporadic PD are reminiscent of what is seen in many common diseases, it is plausible that similar genetic forms could apply to other diseases. Seen in this light, diseases wash in and out of every family, so that in a sense, over time every human family is equally at risk for most diseases.

  1. Angiomyolipoma have common mutations in TSC2 but no other common genetic events.

    Directory of Open Access Journals (Sweden)

    Wei Qin

    Full Text Available Renal angiomyolipoma are part of the PEComa family of neoplasms, and occur both in association with Tuberous Sclerosis Complex (TSC and independent of that disorder. Previous studies on the molecular genetic alterations that occur in angiomyolipoma are very limited. We evaluated 9 angiomyolipoma for which frozen tissue was available from a consecutive surgical series. Seven of 8 samples subjected to RT-PCR-cDNA sequencing showed mutations in TSC2; none showed mutations in TSC1 or RHEB. Six of the seven mutations were deletions. We searched for 983 activating and inactivating mutations in 115 genes, and found none in these tumors. Similarly analysis for genomic regions of loss or gain, assessed by Affymetrix SNP6.0 analysis, showed no abnormalities. Loss of heterozygosity in the TSC2 region was commonly seen, except in patients with low frequency TSC2 mutations. We conclude that sporadic renal angiomyolipoma usually have mutations in TSC2, but not TSC1 or RHEB, and have no other common genomic events, among those we searched for. However, chromosomal translocations and gene fusion events were not assessed here. TSC2 inactivation by mutation is a consistent and likely necessary genetic event in the pathogenesis of most angiomyolipoma.

  2. A rapid genetic assay for the identification of the most common Pocillopora damicornis genetic lineages on the Great Barrier Reef.

    Directory of Open Access Journals (Sweden)

    Gergely Torda

    Full Text Available Pocillopora damicornis (Linnaeus, 1758; Scleractinia, Pocilloporidae has recently been found to comprise at least five distinct genetic lineages in Eastern Australia, some of which likely represent cryptic species. Due to similar and plastic gross morphology of these lineages, field identification is often difficult. Here we present a quick, cost effective genetic assay as well as three novel microsatellite markers that distinguish the two most common lineages found on the Great Barrier Reef. The assay is based on PCR amplification of two regions within the mitochondrial putative control region, which show consistent and easily identifiable fragment size differences for the two genetic lineages after Alu1 restriction enzyme digestion of the amplicons.

  3. Common genetic variants, acting additively, are a major source of risk for autism

    Directory of Open Access Journals (Sweden)

    Klei Lambertus

    2012-10-01

    Full Text Available Abstract Background Autism spectrum disorders (ASD are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex versus multiplex families who have two or more affected individuals. Methods By using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status. Results By analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating. Conclusions Our results, when viewed in the context

  4. Common genetic variability in ESR1 and EGF in relation to endometrial cancer risk and survival

    OpenAIRE

    Einarsdóttir, K; Darabi, H; Czene, K.; Li, Y; Low, Y.L.; Y. Q. Li; Bonnard, C.; Wedrén, S.; Liu, E. T.; Hall, P; Liu, J; Humphreys, K.

    2009-01-01

    We investigated common genetic variation in the entire ESR1 and EGF genes in relation to endometrial cancer risk, myometrial invasion and endometrial cancer survival. We genotyped a dense set of single-nucleotide polymorphisms (SNPs) in both genes and selected haplotype tagging SNPs (tagSNPs). The tagSNPs were genotyped in 713 Swedish endometrial cancer cases and 1567 population controls and the results incorporated into logistic regression and Cox proportional hazards models. We found five a...

  5. Genetic Characterization of Legionella pneumophila Isolated from a Common Watershed in Comunidad Valenciana, Spain.

    Science.gov (United States)

    Sánchez-Busó, Leonor; Coscollá, Mireia; Pinto-Carbó, Marta; Catalán, Vicente; González-Candelas, Fernando

    2013-01-01

    Legionella pneumophila infects humans to produce legionellosis and Pontiac fever only from environmental sources. In order to establish control measures and study the sources of outbreaks it is essential to know extent and distribution of strain variants of this bacterium in the environment. Sporadic and outbreak-related cases of legionellosis have been historically frequent in the Comunidad Valenciana region (CV, Spain), with a high prevalence in its Southeastern-most part (BV). Environmental investigations for the detection of Legionella pneumophila are performed in this area routinely. We present a population genetics study of 87 L. pneumophila strains isolated in 13 different localities of the BV area irrigated from the same watershed and compare them to a dataset of 46 strains isolated in different points of the whole CV. Our goal was to compare environmental genetic variation at two different geographic scales, at county and regional levels. Genetic diversity, recombination and population structure were analyzed with Sequence-Based Typing data and three intergenic regions. The results obtained reveal a low, but detectable, level of genetic differentiation between both datasets, mainly, but not only, attributed to the occurrence of unusual variants of the neuA locus present in the BV populations. This differentiation is still detectable when the 10 loci considered are analyzed independently, despite the relatively high incidence of the most common genetic variant in this species, sequence type 1 (ST-1). However, when the genetic data are considered without their associated geographic information, four major groups could be inferred at the genetic level which did not show any correlation with sampling locations. The overall results indicate that the population structure of these environmental samples results from the joint action of a global, widespread ST-1 along with genetic differentiation at shorter geographic distances, which in this case are related to

  6. Genetic control of the innate immune response

    Directory of Open Access Journals (Sweden)

    Sweet Matthew

    2003-06-01

    Full Text Available Abstract Background Susceptibility to infectious diseases is directed, in part, by the interaction between the invading pathogen and host macrophages. This study examines the influence of genetic background on host-pathogen interactions, by assessing the transcriptional responses of macrophages from five inbred mouse strains to lipopolysaccharide (LPS, a major determinant of responses to gram-negative microorganisms. Results The mouse strains examined varied greatly in the number, amplitude and rate of induction of genes expressed in response to LPS. The response was attenuated in the C3H/HeJlpsd strain, which has a mutation in the LPS receptor Toll-like receptor 4 (TLR4. Variation between mouse strains allowed clustering into early (C57Bl/6J and DBA/2J and delayed (BALB/c and C3H/ARC transcriptional phenotypes. There was no clear correlation between gene induction patterns and variation at the Bcg locus (Slc11A1 or propensity to bias Th1 versus Th2 T cell activation responses. Conclusion Macrophages from each strain responded to LPS with unique gene expression profiles. The variation apparent between genetic backgrounds provides insights into the breadth of possible inflammatory responses, and paradoxically, this divergence was used to identify a common transcriptional program that responds to TLR4 signalling, irrespective of genetic background. Our data indicates that many additional genetic loci control the nature and the extent of transcriptional responses promoted by a single pathogen-associated molecular pattern (PAMP, such as LPS.

  7. Kin-Aggregations Explain Chaotic Genetic Patchiness, a Commonly Observed Genetic Pattern, in a Marine Fish.

    Science.gov (United States)

    Selwyn, Jason D; Hogan, J Derek; Downey-Wall, Alan M; Gurski, Lauren M; Portnoy, David S; Heath, Daniel D

    2016-01-01

    The phenomenon of chaotic genetic patchiness is a pattern commonly seen in marine organisms, particularly those with demersal adults and pelagic larvae. This pattern is usually associated with sweepstakes recruitment and variable reproductive success. Here we investigate the biological underpinnings of this pattern in a species of marine goby Coryphopterus personatus. We find that populations of this species show tell-tale signs of chaotic genetic patchiness including: small, but significant, differences in genetic structure over short distances; a non-equilibrium or "chaotic" pattern of differentiation among locations in space; and within locus, within population deviations from the expectations of Hardy-Weinberg equilibrium (HWE). We show that despite having a pelagic larval stage, and a wide distribution across Caribbean coral reefs, this species forms groups of highly related individuals at small spatial scales (<10 metres). These spatially clustered family groups cause the observed deviations from HWE and local population differentiation, a finding that is rarely demonstrated, but could be more common than previously thought.

  8. [Genetic Structure of Urban Population of the Common Hamster (Cricetus cricetus)].

    Science.gov (United States)

    Feoktistova, N Yu; Meschersky, I G; Surov, A V; Bogomolov, P L; Tovpinetz, N N; Poplavskaya, N S

    2016-02-01

    Over the past half-century, the common hamster (Cricetus cricetus), along with range-wide decline of natural populations, has actively populated the cities. The study of the genetic structure of urban populations of common hamster may shed light on features of the habitation of this species in urban landscapes. This article is focused on the genetic structure of common hamster populations in Simferopol (Crimea), one of the largest known urban populations of this species. On the basis of the analysis of nucleotide sequences of the cytochrome b gene and mtDNA control region, and the allelic composition of ten microsatellite loci of nDNA, we revealed that, despite the fact that some individuals can move throughout the city at considerable distances, the entire population of the city is represented by separate demes confined to different areas. These demes are characterized by a high degree of the genetic isolation and reduced genetic diversity compared to that found for the city as a whole.

  9. Identification of common genetic variation that modulates alternative splicing.

    Directory of Open Access Journals (Sweden)

    Jeremy Hull

    2007-06-01

    Full Text Available Alternative splicing of genes is an efficient means of generating variation in protein function. Several disease states have been associated with rare genetic variants that affect splicing patterns. Conversely, splicing efficiency of some genes is known to vary between individuals without apparent ill effects. What is not clear is whether commonly observed phenotypic variation in splicing patterns, and hence potential variation in protein function, is to a significant extent determined by naturally occurring DNA sequence variation and in particular by single nucleotide polymorphisms (SNPs. In this study, we surveyed the splicing patterns of 250 exons in 22 individuals who had been previously genotyped by the International HapMap Project. We identified 70 simple cassette exon alternative splicing events in our experimental system; for six of these, we detected consistent differences in splicing pattern between individuals, with a highly significant association between splice phenotype and neighbouring SNPs. Remarkably, for five out of six of these events, the strongest correlation was found with the SNP closest to the intron-exon boundary, although the distance between these SNPs and the intron-exon boundary ranged from 2 bp to greater than 1,000 bp. Two of these SNPs were further investigated using a minigene splicing system, and in each case the SNPs were found to exert cis-acting effects on exon splicing efficiency in vitro. The functional consequences of these SNPs could not be predicted using bioinformatic algorithms. Our findings suggest that phenotypic variation in splicing patterns is determined by the presence of SNPs within flanking introns or exons. Effects on splicing may represent an important mechanism by which SNPs influence gene function.

  10. Common Genetic Components of Obesity Traits and Serum Leptin

    DEFF Research Database (Denmark)

    Hasselbalch, Ann L; Benyamin, Beben; Visscher, Peter M

    2008-01-01

    , waist and hip, and skin-fold thickness, body composition assessment by bioimpedance (fat mass and fat-free mass), and measurement of serum leptin level. Bivariate variance component analyses estimated the additive genetic correlations between these measurements. The genetic correlations between...

  11. Genetic Correlation between Body Fat Percentage and Cardiorespiratory Fitness Suggests Common Genetic Etiology

    DEFF Research Database (Denmark)

    Schnurr, Theresia M; Gjesing, Anette P; Sandholt, Camilla H

    2016-01-01

    reflect a common genetic origin. In this study we aimed to 1) examine genetic correlations between body fat% and CRF; 2) determine whether CRF can be attributed to a genetic risk score (GRS) based on known body fat% increasing loci; and 3) examine whether the fat mass and obesity associated (FTO) locus...... of twelve independent risk variants known to associate with body fat%. We assessed CRF as maximal oxygen uptake expressed in millilitres of oxygen uptake per kg of body mass (VO2 max), per kg fat-free mass (VO2 maxFFM ), or per kg fat mass (VO2 maxFM ). All analyses were adjusted for age and sex, and when...... was associated with a 0.42 mL/kg/min unit decrease in VO2 max per allele (p = 0.0092, age and sex adjusted). Both associations were abolished after additional adjustment for body fat %. The fat% increasing GRS and FTO risk allele were associated with decreased VO2 maxFM but not with VO2 maxFFM . Conclusions Our...

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

    Science.gov (United States)

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

    2016-08-01

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

  13. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains.

    Directory of Open Access Journals (Sweden)

    Brian J Bennett

    2015-12-01

    Full Text Available Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP. The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden and human cholesteryl ester transfer protein (CETP. The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear

  14. Common variation in ISL1 confers genetic susceptibility for human congenital heart disease.

    Directory of Open Access Journals (Sweden)

    Kristen N Stevens

    Full Text Available Congenital heart disease (CHD is the most common birth abnormality and the etiology is unknown in the overwhelming majority of cases. ISLET1 (ISL1 is a transcription factor that marks cardiac progenitor cells and generates diverse multipotent cardiovascular cell lineages. The fundamental role of ISL1 in cardiac morphogenesis makes this an exceptional candidate gene to consider as a cause of complex congenital heart disease. We evaluated whether genetic variation in ISL1 fits the common variant-common disease hypothesis. A 2-stage case-control study examined 27 polymorphisms mapping to the ISL1 locus in 300 patients with complex congenital heart disease and 2,201 healthy pediatric controls. Eight genic and flanking ISL1 SNPs were significantly associated with complex congenital heart disease. A replication study analyzed these candidate SNPs in 1,044 new cases and 3,934 independent controls and confirmed that genetic variation in ISL1 is associated with risk of non-syndromic congenital heart disease. Our results demonstrate that two different ISL1 haplotypes contribute to risk of CHD in white and black/African American populations.

  15. Discriminatory power of common genetic variants in personalized breast cancer diagnosis

    Science.gov (United States)

    Wu, Yirong; Abbey, Craig K.; Liu, Jie; Ong, Irene; Peissig, Peggy; Onitilo, Adedayo A.; Fan, Jun; Yuan, Ming; Burnside, Elizabeth S.

    2016-03-01

    Technology advances in genome-wide association studies (GWAS) has engendered optimism that we have entered a new age of precision medicine, in which the risk of breast cancer can be predicted on the basis of a person's genetic variants. The goal of this study is to evaluate the discriminatory power of common genetic variants in breast cancer risk estimation. We conducted a retrospective case-control study drawing from an existing personalized medicine data repository. We collected variables that predict breast cancer risk: 153 high-frequency/low-penetrance genetic variants, reflecting the state-of-the-art GWAS on breast cancer, mammography descriptors and BI-RADS assessment categories in the Breast Imaging Reporting and Data System (BI-RADS) lexicon. We trained and tested naïve Bayes models by using these predictive variables. We generated ROC curves and used the area under the ROC curve (AUC) to quantify predictive performance. We found that genetic variants achieved comparable predictive performance to BI-RADS assessment categories in terms of AUC (0.650 vs. 0.659, p-value = 0.742), but significantly lower predictive performance than the combination of BI-RADS assessment categories and mammography descriptors (0.650 vs. 0.751, p-value < 0.001). A better understanding of relative predictive capability of genetic variants and mammography data may benefit clinicians and patients to make appropriate decisions about breast cancer screening, prevention, and treatment in the era of precision medicine.

  16. Association between Common Genetic Variants and Polycystic Ovary Syndrome Risk in a Chinese Han Population

    Science.gov (United States)

    Sun, Ying; Yuan, Yi; Yang, Hua; Li, Jingjie; Feng, Tian; Ouyang, Yongri; Jin, Tianbo; Liu, Ming

    2016-01-01

    Objective: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting 5-7% of reproductive age women worldwide. The aim of our study was to explore the PCOS-related single nucleotide polymorphism (SNP) associations between common genetic variants and PCOS risk in a Han Chinese women population. Methods: In this case-control study, 285 Chinese Han women aged 28.50±6.858 years with PCOS and 299 controls of a mean age of 32.66±7.018 years were compared. We selected recently published genome-wide association studies (GWAS) which identified several genetic loci in PCOS. All the SNPs were genotyped by Sequenom Mass-ARRAY technology. Associations between the gene and the risk of PCOS were tested using various genetic models by Statistical Package for the Social Sciences and Plink. Results: We found that rs705702 in the RAB5B/SUOX was associated with PCOS (odds ratio=1.42; 95% confidence interval=1.08-1.87, p=0.011) and increased the PCOS risk. The genotypic model analysis also showed that rs705702 was associated with PCOS risk. Conclusion: Our results suggest that SNPs rs705702 in gene RAB5B/SUOX was associated with PCOS in Han Chinese women. PMID:27217259

  17. Genetics in Common Liver Diseases: From Pathophysiology to Precise Treatment.

    Science.gov (United States)

    Lammert, Frank

    In the past 2 decades, advances in genetics have improved our understanding of liver disease and physiology. Firstly, developments in genomic technologies drove the identification of genes responsible for monogenic (Mendelian) liver diseases. Over the last decade, genome-wide association studies allowed for the dissection of the genetic susceptibility to complex liver diseases such as fatty liver disease and drug-induced liver injury, in which environmental co-factors play critical roles. The findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and risk factors and have already pointed to new disease treatments. This is illustrated by the interaction of alcohol, overnutrition and the PNPLA3 gene, which represents an 'infernal triangle' for the liver. In the future, genetics will allow further stratification of liver diseases and contribute to personalized (precision) medicine, offering novel opportunities for translational research and clinical care of our patients. © 2016 S. Karger AG, Basel.

  18. 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.

  19. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivieres, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Loohuis, Loes M. Olde; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santianez, Roberto; Rose, Emma J.; Salami, Alireza; Saemann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Puetz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Goering, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzah, Eva; Melle, Ingrid; Mahnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Muehleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Noethen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdes Hernandez, Maria C.; van't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffman, Wolfgang; Hosten, Norbert; Kahn, Rene S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Mueller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Voelzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Pol, Hilleke E. Hulshoff; Joensson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigat

  20. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    D.P. Hibar (Derrek); J.L. Stein; M.E. Rentería (Miguel); A. Arias-Vásquez (Alejandro); S. Desrivières (Sylvane); N. Jahanshad (Neda); R. Toro (Roberto); K. Wittfeld (Katharina); L. Abramovic (Lucija); M. Andersson (Micael); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); M. Bernard (Manon); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.A. Brown (Andrew); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); G. Cuellar-Partida (Gabriel); A. den Braber (Anouk); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); O. Grimm (Oliver); T. Guadalupe (Tulio); J. Hass (Johanna); G. Woldehawariat (Girma); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil H.); L.M. Olde Loohuis (Loes M.); M. Luciano (Michelle); C. MacAre (Christine); R. Mather; M. Mattheisen (Manuel); Y. Milaneschi (Yuri); K. Nho (Kwangsik); M. Papmeyer (Martina); A. Ramasamy (Adaikalavan); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); E.J. Rose (Emma); A. Salami (Alireza); P.G. Sämann (Philipp); L. Schmaal (Lianne); N.J. Schork (Nicholas); J. Shin (Jean); V.M. Strike (Vanessa); A. Teumer (Alexander); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); R.K. Walters (Raymond); L.T. Westlye (Lars); C.D. Whelan (Christopher); A.M. Winkler (Anderson); M.P. Zwiers (Marcel); S. Alhusaini (Saud); L. Athanasiu (Lavinia); S.M. Ehrlich (Stefan); M. Hakobjan (Marina); C.B. Hartberg (Cecilie B.); U.K. Haukvik (Unn); A.J.G.A.M. Heister (Angelien J. G. A. M.); D. Hoehn (David); D. Kasperaviciute (Dalia); D.C. Liewald (David C.); L.M. Lopez (Lorna); R.R.R. Makkinje (Remco R. R.); M. Matarin (Mar); M.A.M. Naber (Marlies A. M.); D. Reese McKay; M. Needham (Margaret); A.C. Nugent (Allison); B. Pütz (Benno); N.A. Royle (Natalie); L. Shen (Li); R. Sprooten (Roy); D. Trabzuni (Danyah); S.S.L. Van Der Marel (Saskia S. L.); K.J.E. Van Hulzen (Kimm J. E.); E. Walton (Esther); A. Björnsson (Asgeir); L. Almasy (Laura); D. Ames (David); S. Arepalli (Sampath); A.A. Assareh; M.E. Bastin (Mark); H. Brodaty (Henry); K. Bulayeva (Kazima); M.A. Carless (Melanie); S. Cichon (Sven); A. Corvin (Aiden); J.E. Curran (Joanne); M. Czisch (Michael); G.I. de Zubicaray (Greig); A. Dillman (Allissa); A. Duggirala (Aparna); M.D. Dyer (Matthew); S. Erk; I. Fedko (Iryna); L. Ferrucci (Luigi); T. Foroud (Tatiana); P.T. Fox (Peter); M. Fukunaga (Masaki); J. Raphael Gibbs; H.H.H. Göring (Harald H.); R.C. Green (Robert C.); S. Guelfi (Sebastian); N.K. Hansell (Narelle); C.A. Hartman (Catharina); K. Hegenscheid (Katrin); J. Heinz (Judith); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); P.J. Hoekstra (Pieter); F. Holsboer; G. Homuth (Georg); J.J. Hottenga (Jouke Jan); M. Ikeda (Masashi); C.R. Jack Jr. (Clifford); S. Jenkinson (Sarah); R. Johnson (Robert); R. Kanai (Ryota); M. Keil (Maria); J.W. Kent (Jack W.); P. Kochunov (Peter); J.B. Kwok (John B.); S. Lawrie (Stephen); X. Liu (Xinmin); D.L. Longo (Dan L.); K.L. Mcmahon (Katie); E. Meisenzahl (Eva); I. Melle (Ingrid); S. Mohnke (Sebastian); G.W. Montgomery (Grant); J.C. Mostert (Jeanette C.); T.W. Mühleisen (Thomas); M.A. Nalls (Michael); T.E. Nichols (Thomas); L.G. Nilsson; M.M. Nöthen (Markus); K. Ohi (Kazutaka); R.L. Olvera (Rene); R. Perez-Iglesias (Rocio); G. Bruce Pike; S.G. Potkin (Steven); I. Reinvang (Ivar); S. Reppermund; M. Rietschel (M.); N. Seiferth (Nina); G.D. Rosen (Glenn D.); D. Rujescu (Dan); K. Schnell (Kerry); C.J. Schofield (Christopher); C. Smith (Colin); V.M. Steen (Vidar); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); J. Turner (Jessica); M.C. Valdés Hernández (Maria); D. van 't Ent (Dennis); M.P. van der Brug (Marcel); N.J. van der Wee (Nic); M.J.D. van Tol (Marie-José); D.J. Veltman (Dick); A.M.J. Wassink (Annemarie); E. Westman (Eric); R.H. Zielke (Ronald H.); A.B. Zonderman (Alan B.); D.G. Ashbrook (David G.); R. Hager (Reinmar); L. Lu (Lu); F.J. Mcmahon (Francis J); D.W. Morris (Derek W); R.W. Williams (Robert W.); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan K.); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); G. Cavalleri (Gianpiero); B. Crespo-Facorro (Benedicto); A.M. Dale (Anders); G.E. Davies (Gareth); N. Delanty; C. Depondt (Chantal); S. Djurovic (Srdjan); D.A. Drevets (Douglas); T. Espeseth (Thomas); R.L. Gollub (Randy); B.C. Ho (Beng ); W. Hoffmann (Wolfgang)

    2015-01-01

    textabstractThe highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate

  1. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivieres, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Loohuis, Loes M. Olde; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santianez, Roberto; Rose, Emma J.; Salami, Alireza; Saemann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Puetz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Goering, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzah, Eva; Melle, Ingrid; Mahnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Muehleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Noethen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdes Hernandez, Maria C.; van't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffman, Wolfgang; Hosten, Norbert; Kahn, Rene S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Mueller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Voelzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Pol, Hilleke E. Hulshoff; Joensson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To

  2. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    D.P. Hibar (Derrek); J.L. Stein; M.E. Rentería (Miguel); A. Arias-Vásquez (Alejandro); S. Desrivières (Sylvane); N. Jahanshad (Neda); R. Toro (Roberto); K. Wittfeld (Katharina); L. Abramovic; M. Andersson (Micael); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); M. Bernard (Manon); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.A. Brown (Andrew); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); G. Cuellar-Partida (Gabriel); A. den Braber (Anouk); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); O. Grimm (Oliver); T. Guadalupe (Tulio); J. Hass (Johanna); G. Woldehawariat (Girma); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil H.); L.M. Olde Loohuis (Loes M.); M. Luciano (Michelle); C. MacAre (Christine); R. Mather; M. Mattheisen (Manuel); Y. Milaneschi (Yuri); K. Nho (Kwangsik); M. Papmeyer (Martina); A. Ramasamy (Adaikalavan); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); E.J. Rose (Emma); A. Salami (Alireza); P.G. Sämann (Philipp); L. Schmaal (Lianne); N.J. Schork (Nicholas); J. Shin (Jean); V.M. Strike (Vanessa); A. Teumer (Alexander); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); R.K. Walters (Raymond); L.T. Westlye (Lars); C.D. Whelan (Christopher); A.M. Winkler (Anderson); M.P. Zwiers (Marcel); S. Alhusaini (Saud); L. Athanasiu (Lavinia); S.M. Ehrlich (Stefan); M. Hakobjan (Marina); C.B. Hartberg (Cecilie B.); U.K. Haukvik (Unn); A.J.G.A.M. Heister (Angelien J. G. A. M.); D. Hoehn (David); D. Kasperaviciute (Dalia); D.C. Liewald (David C.); L.M. Lopez (Lorna); R.R.R. Makkinje (Remco R. R.); M. Matarin (Mar); M.A.M. Naber (Marlies A. M.); D. Reese McKay; M. Needham (Margaret); A.C. Nugent (Allison); B. Pütz (Benno); N.A. Royle (Natalie); L. Shen (Li); R. Sprooten (Roy); D. Trabzuni (Danyah); S.S.L. Van Der Marel (Saskia S. L.); K.J.E. Van Hulzen (Kimm J. E.); E. Walton (Esther); A. Björnsson (Asgeir); L. Almasy (Laura); D. Ames (David); S. Arepalli (Sampath); A.A. Assareh; M.E. Bastin (Mark); H. Brodaty (Henry); K. Bulayeva (Kazima); M.A. Carless (Melanie); S. Cichon (Sven); A. Corvin (Aiden); J.E. Curran (Joanne); M. Czisch (Michael); G.I. de Zubicaray (Greig); A. Dillman (Allissa); A. Duggirala (Aparna); M.D. Dyer (Matthew); S. Erk; I. Fedko (Iryna); L. Ferrucci (Luigi); T. Foroud (Tatiana); P.T. Fox (Peter); M. Fukunaga (Masaki); J. Raphael Gibbs; H.H.H. Göring (Harald H.); R.C. Green (Robert C.); S. Guelfi (Sebastian); N.K. Hansell (Narelle); C.A. Hartman (Catharina); K. Hegenscheid (Katrin); J. Heinz (Judith); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); P.J. Hoekstra (Pieter); F. Holsboer; G. Homuth (Georg); J.J. Hottenga (Jouke Jan); M. Ikeda (Masashi); C.R. Jack Jr. (Clifford); S. Jenkinson (Sarah); R. Johnson (Robert); R. Kanai (Ryota); M. Keil (Maria); J.W. Kent (Jack W.); P. Kochunov (Peter); J.B. Kwok (John B.); S. Lawrie (Stephen); X. Liu (Xinmin); D.L. Longo (Dan L.); K.L. Mcmahon (Katie); E. Meisenzahl (Eva); I. Melle (Ingrid); S. Mohnke (Sebastian); G.W. Montgomery (Grant); J.C. Mostert (Jeanette C.); T.W. Mühleisen (Thomas); M.A. Nalls (Michael); T.E. Nichols (Thomas); L.G. Nilsson; M.M. Nöthen (Markus); K. Ohi (Kazutaka); R.L. Olvera (Rene); R. Perez-Iglesias (Rocio); G. Bruce Pike; S.G. Potkin (Steven); I. Reinvang (Ivar); S. Reppermund; M. Rietschel (M.); N. Seiferth (Nina); G.D. Rosen (Glenn D.); D. Rujescu (Dan); K. Schnell (Kerry); C.J. Schofield (Christopher); C. Smith (Colin); V.M. Steen (Vidar); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); J. Turner (Jessica); M.C. Valdés Hernández (Maria); D. van 't Ent (Dennis); M.P. van der Brug (Marcel); N.J. van der Wee (Nic); M.J.D. van Tol (Marie-José); D.J. Veltman (Dick); A.M.J. Wassink (Annemarie); E. Westman (Eric); R.H. Zielke (Ronald H.); A.B. Zonderman (Alan B.); D.G. Ashbrook (David G.); R. Hager (Reinmar); L. Lu (Lu); F.J. Mcmahon (Francis J); D.W. Morris (Derek W); R.W. Williams (Robert W.); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan K.); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); G. Cavalleri (Gianpiero); B. Crespo-Facorro (Benedicto); A.M. Dale (Anders); G.E. Davies (Gareth); N. Delanty; C. Depondt (Chantal); S. Djurovic (Srdjan); D.A. Drevets (Douglas); T. Espeseth (Thomas); R.L. Gollub (Randy); B.C. Ho (Beng ); W. Hoffmann (Wolfgang); N. Hosten (Norbert); R. Kahn; S. Le Hellard (Stephanie); A. Meyer-Lindenberg; B. Müller-Myhsok (B.); M. Nauck (Matthias); L. Nyberg (Lars); M. Pandolfo (Massimo); B.W.J.H. Penninx (Brenda); J.L. Roffman (Joshua); S.M. Sisodiya (Sanjay); J.W. Smoller; H. van Bokhoven (Hans); N.E.M. van Haren (Neeltje E.); H. Völzke (Henry); H.J. Walter (Henrik); M.W. Weiner (Michael); W. Wen (Wei); T.J.H. White (Tonya); I. Agartz (Ingrid); O.A. Andreassen (Ole A.); J. Blangero (John); D.I. Boomsma (Dorret); R.M. Brouwer (Rachel); D.M. Cannon (Dara); M.R. Cookson (Mark); E.J.C. de Geus (Eco); I.J. Deary (Ian J.); D.J. Donohoe (Dennis); G. Fernandez (Guillén); S.E. Fisher (Simon); C. Francks (Clyde); D.C. Glahn (David); H.J. Grabe (Hans Jörgen); O. Gruber (Oliver); J. Hardy (John); R. Hashimoto (Ryota); H.E. Hulshoff Pol (Hilleke); E.G. Jönsson (Erik); I. Kloszewska (Iwona); S. Lovestone (Simon); V.S. Mattay (Venkata S.); P. Mecocci (Patrizia); C. McDonald (Colm); A.M. McIntosh (Andrew); R.A. Ophoff (Roel); T. Paus (Tomas); Z. Pausova (Zdenka); M. Ryten (Mina); P.S. Sachdev (Perminder); A.J. Saykin (Andrew); A. Simmons (Andrew); A. Singleton (Andrew); H. Soininen (H.); J.M. Wardlaw (J.); M.E. Weale (Michael); D.R. Weinberger (Daniel); H.H.H. Adams (Hieab); L.J. Launer (Lenore); S. Seiler (Stephan); R. Schmidt (Reinhold); G. Chauhan (Ganesh); C.L. Satizabal (Claudia L.); J.T. Becker (James); L.R. Yanek (Lisa); S. van der Lee (Sven); M. Ebling (Maritza); B. Fischl (Bruce); W.T. Longstreth Jr; D. Greve (Douglas); R. Schmidt (Reinhold); P. Nyquist (Paul); L.N. Vinke (Louis N.); C.M. van Duijn (Cock); L. Xue (Luting); B. Mazoyer (Bernard); J.C. Bis (Joshua); V. Gudnason (Vilmundur); S. Seshadri (Sudha); M.A. Ikram (Arfan); N.G. Martin (Nicholas); M.J. Wright (Margaret); G. Schumann (Gunter); B. Franke (Barbara); P.M. Thompson (Paul); S.E. Medland (Sarah Elizabeth)

    2015-01-01

    textabstractThe highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate h

  3. Genetics and Common Disorders: Implications for Primary Care and Public Health Providers

    Energy Technology Data Exchange (ETDEWEB)

    McInerney, Joseph D.; Greendale, Karen; Peay, Holly L.

    2005-06-01

    We developed this program for primary care providers (PCPs) and public health professionals (PHPs) who are interested in increasing their understanding of the genetics of common chronic diseases and of the implications of genetics and genomics for their fields. The program differs from virtually all previous educational efforts in genetics for health professionals in that it focuses on the genetics of common chronic disease and on the broad principles that emerge when one views disease from the perspectives of variation and individuality, which are at the heart of thinking genetically. The CD-ROM introduces users to content that will improve their understanding of topics such as: • A framework for genetics and common disease; • Basic information on genetics, genomics, genetic medicine, and public health genetics, all in the context of common chronic disease; • The status of research on genetic contributions to specific common diseases, including a review of research methods; • Genetic/environmental interaction as the new “central dogma” of public health genetics; • The importance of taking and analyzing a family history; • The likely impact of potential gene discovery and genetic testing on genetic counseling and risk assessment and on the practices of PCPs and PHPs; • Stratification of populations into low-, moderate-, and high-risk categories; • The potential role of PCPs and PHPs in identifying high-risk individuals and families, in providing limited genetics services, and in referring to clinical genetics specialists; the potential for standard referral algorithms; • Implications of genetic insights for diagnosis and treatment; • Ethical, legal, and social issues that arise from genetic testing for common chronic diseases; and • Specific prevention strategies based on understanding of genetics and genetic/ environmental interactions. The interactive content – developed by experts in genetics, primary care, and public health – is

  4. Systems genetics view of endometriosis: a common complex disorder.

    Science.gov (United States)

    Baranov, Vladislav S; Ivaschenko, Tatyana E; Liehr, Thomas; Yarmolinskaya, Maria I

    2015-02-01

    Endometriosis is a condition in which cells derived from the endometrium grow outside the uterus, e.g. in the peritoneum (external genital endometriosis). As these cells are under the influence of female hormones, major symptoms of endometriosis are pain, especially during the cycle, and infertility. Numerous hypotheses for the formation of endometriosis can be found in the literature, but there is growing evidence of serious genetic contributions to endometriosis susceptibility. The involvement of genes, steroid hormone metabolism, immunological reactions, receptor formation, inflammation, proliferation, apoptosis, intercellular adhesion, cell invasion and angiogenesis as well as genes regulating the activity of aforementioned enzymes have been suggested. Some more recently suggested candidate genes picked up in genome-wide association studies are involved in oncogenesis, metaplasia of endometrium cells and pathways of embryonic development of the female reproductive system. However, gene mutations proven to be causative for endometriosis have not been identified so far, even though the abnormal expression of candidate genes for endometriosis could be provoked by different epigenetic modifications including DNA methylation, heterochromatization or introduction of regulatory miRNA. We hypothesize that endometriosis is induced by a combination of abnormal genetic and/or epigenetic mutations: the latter pave the way for pathological changes which become irreversible, and according to the "epigenetic landscape" theory, this proceeds to the typical clinical manifestations. Two stages in the endometriosis pathway are suggested: (1) induction of primary endometrial cells toward endometriosis, and (2) implantation and progression of these cells into endometriosis lesions. The model favors endometriosis as an outgrowth of primary cells different in their origin, canalization of pathological processes, manifestation diversity provoked by unique genetic background and

  5. Feline and canine coronaviruses: common genetic and pathobiological features.

    Science.gov (United States)

    Le Poder, Sophie

    2011-01-01

    A new human coronavirus responsible for severe acute respiratory syndrome (SARS) was identified in 2003, which raised concern about coronaviruses as agents of serious infectious disease. Nevertheless, coronaviruses have been known for about 50 years to be major agents of respiratory, enteric, or systemic infections of domestic and companion animals. Feline and canine coronaviruses are widespread among dog and cat populations, sometimes leading to the fatal diseases known as feline infectious peritonitis (FIP) and pantropic canine coronavirus infection in cats and dogs, respectively. In this paper, different aspects of the genetics, host cell tropism, and pathogenesis of the feline and canine coronaviruses (FCoV and CCoV) will be discussed, with a view to illustrating how study of FCoVs and CCoVs can improve our general understanding of the pathobiology of coronaviruses.

  6. Feline and Canine Coronaviruses: Common Genetic and Pathobiological Features

    Directory of Open Access Journals (Sweden)

    Sophie Le Poder

    2011-01-01

    Full Text Available A new human coronavirus responsible for severe acute respiratory syndrome (SARS was identified in 2003, which raised concern about coronaviruses as agents of serious infectious disease. Nevertheless, coronaviruses have been known for about 50 years to be major agents of respiratory, enteric, or systemic infections of domestic and companion animals. Feline and canine coronaviruses are widespread among dog and cat populations, sometimes leading to the fatal diseases known as feline infectious peritonitis (FIP and pantropic canine coronavirus infection in cats and dogs, respectively. In this paper, different aspects of the genetics, host cell tropism, and pathogenesis of the feline and canine coronaviruses (FCoV and CCoV will be discussed, with a view to illustrating how study of FCoVs and CCoVs can improve our general understanding of the pathobiology of coronaviruses.

  7. The association between common genetic variation in the FTO gene and metabolic syndrome in Han Chinese

    Institute of Scientific and Technical Information of China (English)

    WANG Tong; ZHANG Li-li; ZHANG Yun; SUN Xiao-fang; ZHANG Qian; HUANG Yi; XIAO Xin-hua; WANG Duen-mei; DIAO Cheng-ming; ZHANG Feng; XU Ling-ling; ZHANG Yong-biao; LI Wen-hui

    2010-01-01

    Background Genome-wide association studies for type 2 diabetes mellitus (T2DM) identified FTO gene as a locus conferring increased risk for common obesity in many populations with European ancestry. However, the involvement of FTO gene in obesity or T2DM related metabolic traits has not been consistently established in Chinese populations. The objective of this study was to investigate the association of FTO genetic polymorphisms with metabolic syndrome (MetS) in Han Chinese.Methods We tested 41 FTO single nucleotide polymorphisms (SNPs) for association between FTO and MetS-related traits. There were a total of 236 unrelated subjects (108 cases and 128 controls), grouped according to the International Diabetes Federation (IDF) criteria.Results Of the 41 SNPs examined, only SNP rs8047395 exhibited statistical significance (P=0.026) under a recessive model, after Bonferroni adjustment for multiple testing (OR 1.64, 95% CI 1.11-2.42; P=0.014). The common distributions of this polymorphism among Chinese-with a minor allele frequency (MAF) of 36% in the control group versus 48% in the MetS group-greatly improved our test power in a relatively small sample size for an association study. Previously identified obesity-(or T2DM-) associated FTO SNPs were less common in Han Chinese and were not associated with MetS in this study. No significant associations were found between our FTO SNPs and any endophenotypes of MetS.Conclusions A more common risk-conferring variant of FTO for MetS was identified in Han Chinese. Our study substantiated that genetic variations in FTO locus are involved in the pathogenesis of MetS.

  8. Understanding genetic information as a commons: From bioprospecting to personalized medicine

    Directory of Open Access Journals (Sweden)

    Nicola Lucchi

    2013-08-01

    Full Text Available The aim of the paper is to discuss how the concept of commons can be enlarged to include genetic resources – both naturally occurring and as essential resources in research laboratories – that are increasingly considered as part of market frameworks. Looking beyond the enclosure of traditional public goods (such as land or water, the paper emphasizes the debate around the progressive commodification of genetic resources and associated genetic information operated by means of intellectual property rights or other forms of management of knowledge. The discourse around commons is used to evaluate alternative tools and strategies to the issue of private appropriation of human genetic resources and natural compounds.

  9. Premature birth and diseases in premature infants: common genetic background?

    Science.gov (United States)

    Hallman, Mikko

    2012-04-01

    It has been proposed that during human evolution, development of obligate bipedalism, narrow birth canal cross-sectional area and the large brain have forced an adjustment in duration of pregnancy (scaling of gestational age; Plunkett 2011). Children compared to other mammals are born with proportionally small brains (compared to adult brains), suggesting shortening of pregnancy duration during recent evolution. Prevalence of both obstructed delivery and premature birth is still exceptionally high. In near term infants, functional maturity and viability is high, and gene variants predisposing to respiratory distress syndrome (RDS) are rare. Advanced antenatal and neonatal treatment practices during the new era of medicine allowed survival of also very preterm infants (gestation premature birth. Specific genes associating with diseases in preterm infants may also contribute to the susceptibility to preterm birth. Understanding and applying the knowledge of genetic interactions in normal and abnormal perinatal-neonatal development requires large, well-structured population cohorts, studies involving the whole genome and international interdisciplinary collaboration.

  10. Population genetics of invasive common carp Cyprinus carpio L. in coastal drainages in eastern Australia.

    Science.gov (United States)

    Haynes, G D; Gilligan, D M; Grewe, P; Moran, C; Nicholas, F W

    2010-10-01

    The common carp Cyprinus carpio introduced in two drainages in eastern Australia are largely descended from European common carp, and in a third drainage they descend largely from East Asian common carp. The partial genetic differentiation among the species in those drainages is consistent with their origins.

  11. Development and application of genetically uniform strains of common carp (Cyprinus carpio L.)

    NARCIS (Netherlands)

    Bongers, A.B.J.

    1997-01-01

    In this thesis, the development of genetically uniform strains of common carp, Cyprinus carpio L. is described. As in research on mammals, the use of genetically uniform fish could increase the quality (replicability, reproducability and repeatability) of experiments. Inbreeding was done by gynogene

  12. Functional complementation studies identify candidate genes and common genetic variants associated with ovarian cancer survival

    DEFF Research Database (Denmark)

    Quaye, Lydia; Dafou, Dimitra; Ramus, Susan J;

    2009-01-01

    Common germline genetic variation and/or somatic alterations in tumours may be associated with survival in women diagnosed with ovarian cancer. The successful identification of genetic associations relies on a suitable strategy for identifying and testing candidate genes. We used microcell-mediat...

  13. Glioblastomas with Oligodendroglial Component – Common Origin of the Different Histological Parts and Genetic Subclassification

    Directory of Open Access Journals (Sweden)

    Barbara Klink

    2010-01-01

    Full Text Available Background: Glioblastomas are the most common and most malignant brain tumors in adults. A small subgroup of glioblastomas contains areas with histological features of oligodendroglial differentiation (GBMO. Our objective was to genetically characterize the oligodendroglial and the astrocytic parts of GBMOs and correlate morphologic and genetic features with clinical data.

  14. A Comprehensive Analysis of Common Genetic Variation Around Six Candidate Loci for Intrahepatic Cholestasis of Pregnancy

    Science.gov (United States)

    Dixon, Peter H; Wadsworth, Christopher A; Chambers, Jennifer; Donnelly, Jennifer; Cooley, Sharon; Buckley, Rebecca; Mannino, Ramona; Jarvis, Sheba; Syngelaki, Argyro; Geenes, Victoria; Paul, Priyadarshini; Sothinathan, Meera; Kubitz, Ralf; Lammert, Frank; Tribe, Rachel M; Ch'ng, Chin Lye; Marschall, Hanns-Ulrich; Glantz, Anna; Khan, Shahid A; Nicolaides, Kypros; Whittaker, John; Geary, Michael; Williamson, Catherine

    2014-01-01

    OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) has a complex etiology with a significant genetic component. Heterozygous mutations of canalicular transporters occur in a subset of ICP cases and a population susceptibility allele (p.444A) has been identified in ABCB11. We sought to expand our knowledge of the detailed genetic contribution to ICP by investigation of common variation around candidate loci with biological plausibility for a role in ICP (ABCB4, ABCB11, ABCC2, ATP8B1, NR1H4, and FGF19). METHODS: ICP patients (n=563) of white western European origin and controls (n=642) were analyzed in a case–control design. Single-nucleotide polymorphism (SNP) markers (n=83) were selected from the HapMap data set (Tagger, Haploview 4.1 (build 22)). Genotyping was performed by allelic discrimination assay on a robotic platform. Following quality control, SNP data were analyzed by Armitage's trend test. RESULTS: Cochran–Armitage trend testing identified six SNPs in ABCB11 together with six SNPs in ABCB4 that showed significant evidence of association. The minimum Bonferroni corrected P value for trend testing ABCB11 was 5.81×10−4 (rs3815676) and for ABCB4 it was 4.6×10−7(rs2109505). Conditional analysis of the two clusters of association signals suggested a single signal in ABCB4 but evidence for two independent signals in ABCB11. To confirm these findings, a second study was performed in a further 227 cases, which confirmed and strengthened the original findings. CONCLUSIONS: Our analysis of a large cohort of ICP cases has identified a key role for common variation around the ABCB4 and ABCB11 loci, identified the core associations, and expanded our knowledge of ICP susceptibility. PMID:24366234

  15. Common variants of the PINK1 and PARL genes do not confer genetic susceptibility to schizophrenia in Han Chinese.

    Science.gov (United States)

    Li, Xiao; Zhang, Wen; Zhang, Chen; Yi, Zhenghui; Zhang, Deng-Feng; Gong, Wei; Tang, Jinsong; Wang, Dong; Lu, Weihong; Chen, Xiaogang; Fang, Yiru; Yao, Yong-Gang

    2015-04-01

    Schizophrenia is a prevalent psychiatric disorder with a complex etiology. Mitochondrial dysfunction has been frequently reported in schizophrenia. Phosphatase and tension homologue-induced kinase 1 (PINK1) and presenilin-associated rhomboid-like protease (PARL) are mitochondrial proteins, and genetic variants of these two genes may confer genetic susceptibility to schizophrenia by influencing mitochondrial function. In this study, we conducted a two-stage genetic association study to test this hypothesis. We genotyped 4 PINK1 and 5 PARL genetic variants and evaluated the potential association of the 9 SNPs with schizophrenia in two independent case-control cohorts of 2510 Han Chinese individuals. No positive association of common genetic variants of the PINK1 and PARL genes with schizophrenia was identified in our samples after Bonferroni correction. Re-analysis of the newly updated Psychiatric Genetics Consortium (PGC) data sets confirmed our negative result. Intriguingly, one PINK1 SNP (rs10916832), which showed a marginally significant association in only Hunan samples (P = 0.032), is associated with the expression of a schizophrenia susceptible gene KIF17 according to the expression quantitative trait locus (eQTL) analysis. Our study indicated that common genetic variants of the PINK1 and PARL genes are unlikely to be involved in schizophrenia. Further studies are essential to characterize the role of the PINK1 and PARL genes in schizophrenia.

  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. Governing the management and use of pooled microbial genetic resources: Lessons from the global crop commons

    Directory of Open Access Journals (Sweden)

    Michael Halewood

    2010-01-01

    Full Text Available The paper highlights lessons learned over the last thirty years establishing a governance structure for the global crop commons that are of relevance to current champions of the microbial commons. It argues that the political, legal and biophysical situation in which microbial genetic resources (and their users are located today are similar to the situation of plant genetic resources in the mid-1990s, before the International Treaty on Plant Genetic Resources was negotiated. Consequently, the paper suggests that it may be useful to look to the model of global network of ex situ plant genetic resources collections as a precedent to follow – even if only loosely – in developing an intergovernmentally endorsed legal substructure and governance framework for the microbial commons.

  18. PRELIMINARY ANALYSIS OF COMMON LOON GENETIC STRUCTURE IN NORTH AMERICA BASED ON FIVE MICROSATELLITE LOCI

    Science.gov (United States)

    This study seeks to determine fine-scale genetic structure of Common Loon breeding populations in order to link wintering birds with their breeding regions. Common Loons are large piscivorous birds that breed in lakes of northern North America and Iceland. Loons are highly phil...

  19. Common TLR1 genetic variation is not associated with death from melioidosis, a common cause of sepsis in rural Thailand.

    Directory of Open Access Journals (Sweden)

    Narisara Chantratita

    Full Text Available Melioidosis, infection caused by the Gram-negative bacterium Burkholderia pseudomallei, is a common cause of sepsis in northeast Thailand. In white North Americans, common functional genetic variation in TLR1 is associated with organ failure and death from sepsis. We hypothesized that TLR1 variants would be associated with outcomes in Thais with melioidosis. We collated the global frequencies of three TLR1 variants that are common in white North American populations: rs5743551 (-7202A/G, rs4833095 (742A/G, and rs5743618 (1804G/T. We noted a reversal of the minor allele from white North American subjects to Asian populations that was particularly pronounced for rs5743618. In the Utah residents of European ancestry, the frequency of the rs5743618 T allele was 17% whereas in Vietnamese subjects the frequency was >99%. We conducted a genetic association study in 427 patients with melioidosis to determine the association of TLR1 variation with organ failure or death. We genotyped rs5743551 and rs4833095. The variants were in high linkage disequilibrium but neither variant was associated with organ failure or in-hospital death. In 300 healthy Thai individuals we further tested the association of TLR1 variation with ex vivo blood responses to Pam3CSK4, a TLR1 agonist. Neither variant was robustly associated with blood cytokine responses induced by Pam3CSK4. We identified additional common variation in TLR1 by searching public databases and the published literature and screened three additional TLR1 variants for associations with Pam3CSK4-induced responses but found none. We conclude that the genetic architecture of TLR1 variation differs substantially in southeast Asians compared to other populations and common variation in TLR1 in Thais is not associated with outcome from melioidosis or with altered blood responses to Pam3CSK4. Our findings highlight the need for additional studies of TLR1 and other innate immune genetic modulators of the inflammatory

  20. Cyclostationary signature design for common control channel of cognitive radio

    Institute of Scientific and Technical Information of China (English)

    QI Yuan; PENG Tao; WANG Wen-bo; LUO Shi-feng

    2009-01-01

    Embedding specific signatures in transmitted signals for identifying common control channels of cognitive radio are addressed in research laboratories because availability of the spectrum occupied by the common control channel might change in time. A novel solution to embed a unique cyclostationary signature for the common control channel of cognitive radio is proposed in this article. Based on linear periodically time-variant transformation (LPTV) model, the cyclic autocorrelation expression of the proposed signature is derived, which characterizes its cyclostationarity. Analysis of the cyclostationary signature is presented considering effects of additive white Gaussian noise(AWGN)and multiplath channels. Simulation results illustrating the reliability of signatures are given.

  1. Intraspecific morphological and genetic variation of common species predicts ranges of threatened ones

    Science.gov (United States)

    Fuller, Trevon L.; Thomassen, Henri A.; Peralvo, Manuel; Buermann, Wolfgang; Milá, Borja; Kieswetter, Charles M.; Jarrín-V, Pablo; Devitt, Susan E. Cameron; Mason, Eliza; Schweizer, Rena M.; Schlunegger, Jasmin; Chan, Janice; Wang, Ophelia; Schneider, Christopher J.; Pollinger, John P.; Saatchi, Sassan; Graham, Catherine H.; Wayne, Robert K.; Smith, Thomas B.

    2013-01-01

    Predicting where threatened species occur is useful for making informed conservation decisions. However, because they are usually rare, surveying threatened species is often expensive and time intensive. Here, we show how regions where common species exhibit high genetic and morphological divergence among populations can be used to predict the occurrence of species of conservation concern. Intraspecific variation of common species of birds, bats and frogs from Ecuador were found to be a significantly better predictor for the occurrence of threatened species than suites of environmental variables or the occurrence of amphibians and birds. Fully 93 per cent of the threatened species analysed had their range adequately represented by the geographical distribution of the morphological and genetic variation found in seven common species. Both higher numbers of threatened species and greater genetic and morphological variation of common species occurred along elevation gradients. Higher levels of intraspecific divergence may be the result of disruptive selection and/or introgression along gradients. We suggest that collecting data on genetic and morphological variation in common species can be a cost effective tool for conservation planning, and that future biodiversity inventories include surveying genetic and morphological data of common species whenever feasible. PMID:23595273

  2. Hybrid Genetic Algorithms with Fuzzy Logic Controller

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In this paper, a new implementation of genetic algorithms (GAs) is developed for the machine scheduling problem, which is abundant among the modern manufacturing systems. The performance measure of early and tardy completion of jobs is very natural as one's aim, which is usually to minimize simultaneously both earliness and tardiness of all jobs. As the problem is NP-hard and no effective algorithms exist, we propose a hybrid genetic algorithms approach to deal with it. We adjust the crossover and mutation probabilities by fuzzy logic controller whereas the hybrid genetic algorithm does not require preliminary experiments to determine probabilities for genetic operators. The experimental results show the effectiveness of the GAs method proposed in the paper.``

  3. Genetic diversity in cultivated carioca common beans based on molecular marker analysis

    Directory of Open Access Journals (Sweden)

    Juliana Morini Küpper Cardoso Perseguini

    2011-01-01

    Full Text Available A wide array of molecular markers has been used to investigate the genetic diversity among common bean species. However, the best combination of markers for studying such diversity among common bean cultivars has yet to be determined. Few reports have examined the genetic diversity of the carioca bean, commercially one of the most important common beans in Brazil. In this study, we examined the usefulness of two molecular marker systems (simple sequence repeats - SSRs and amplified fragment length polymorphisms - AFLPs for assessing the genetic diversity of carioca beans. The amount of information provided by Roger's modified genetic distance was used to analyze SSR data and Jaccards similarity coefficient was used for AFLP data. Seventy SSRs were polymorphic and 20 AFLP primer combinations produced 635 polymorphic bands. Molecular analysis showed that carioca genotypes were quite diverse. AFLPs revealed greater genetic differentiation and variation within the carioca genotypes (Gst = 98% and Fst = 0.83, respectively than SSRs and provided better resolution for clustering the carioca genotypes. SSRs and AFLPs were both suitable for assessing the genetic diversity of Brazilian carioca genotypes since the number of markers used in each system provided a low coefficient of variation. However, fingerprint profiles were generated faster with AFLPs, making them a better choice for assessing genetic diversity in the carioca germplasm.

  4. Common genetic architecture underlying young children's food fussiness and liking for vegetables and fruit.

    Science.gov (United States)

    Fildes, Alison; van Jaarsveld, Cornelia H M; Cooke, Lucy; Wardle, Jane; Llewellyn, Clare H

    2016-04-01

    Food fussiness (FF) is common in early childhood and is often associated with the rejection of nutrient-dense foods such as vegetables and fruit. FF and liking for vegetables and fruit are likely all heritable phenotypes; the genetic influence underlying FF may explain the observed genetic influence on liking for vegetables and fruit. Twin analyses make it possible to get a broad-based estimate of the extent of the shared genetic influence that underlies these traits. We quantified the extent of the shared genetic influence that underlies FF and liking for vegetables and fruit in early childhood with the use of a twin design. Data were from the Gemini cohort, which is a population-based sample of twins born in England and Wales in 2007. Parents of 3-y-old twins (n= 1330 pairs) completed questionnaire measures of their children's food preferences (liking for vegetables and fruit) and the FF scale from the Children's Eating Behavior Questionnaire. Multivariate quantitative genetic modeling was used to estimate common genetic influences that underlie FF and liking for vegetables and fruit. Genetic correlations were significant and moderate to large in size between FF and liking for both vegetables (-0.65) and fruit (-0.43), which indicated that a substantial proportion of the genes that influence FF also influence liking. Common genes that underlie FF and liking for vegetables and fruit largely explained the observed phenotypic correlations between them (68-70%). FF and liking for fruit and vegetables in young children share a large proportion of common genetic factors. The genetic influence on FF may determine why fussy children typically reject fruit and vegetables.

  5. Common Occupational Health Problems In Disease Control In Nigeria

    African Journals Online (AJOL)

    Common Occupational Health Problems In Disease Control In Nigeria. ... laboratories, hazardous gases like ethylene oxide and nitrous oxides; physical agents like ... When duely exposed, health workers are at high risk of health problems like ...

  6. Genetic control of cuticular wax compounds in Eucalyptus globulus.

    Science.gov (United States)

    Gosney, Benjamin J; Potts, Brad M; O'Reilly-Wapstra, Julianne M; Vaillancourt, René E; Fitzgerald, Hugh; Davies, Noel W; Freeman, Jules S

    2016-01-01

    Plant cuticular wax compounds perform functions that are essential for the survival of terrestrial plants. Despite their importance, the genetic control of these compounds is poorly understood outside of model taxa. Here we investigate the genetic basis of variation in cuticular compounds in Eucalyptus globulus using quantitative genetic and quantitative trait loci (QTL) analyses. Quantitative genetic analysis was conducted using 246 open-pollinated progeny from 13 native sub-races throughout the geographic range. QTL analysis was conducted using 112 clonally replicated progeny from an outcross F2 population. Nine compounds exhibited significant genetic variation among sub-races with three exhibiting signals of diversifying selection. Fifty-two QTL were found with co-location of QTL for related compounds commonly observed. Notable among these was the QTL for five wax esters, which co-located with a gene from the KCS family, previously implicated in the biosynthesis of cuticular waxes in Arabidopsis. In combination, the QTL and quantitative genetic analyses suggest the variation and differentiation in cuticular wax compounds within E. globulus has a complex genetic origin. Sub-races exhibited independent latitudinal and longitudinal differentiation in cuticular wax compounds, likely reflecting processes such as historic gene flow and diversifying selection acting upon genes that have diverse functions in distinct biochemical pathways.

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

    Science.gov (United States)

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

    2015-09-15

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

  8. Genetic mapping of two genes conferring resistance to powdery mildew in common bean (Phaseolus vulgaris L.).

    Science.gov (United States)

    Pérez-Vega, Elena; Trabanco, Noemí; Campa, Ana; Ferreira, Juan José

    2013-06-01

    Powdery mildew (PM) is a serious disease in many legume species, including the common bean (Phaseolus vulgaris L.). This study investigated the genetic control behind resistance reaction to PM in the bean genotype, Cornell 49242. The results revealed evidence supporting a qualitative mode of inheritance for resistance and the involvement of two independent genes in the resistance reaction. The location of these resistance genes was investigated in a linkage genetic map developed for the XC RIL population. Contingency tests revealed significant associations for 28 loci out of a total of 329 mapped loci. Fifteen were isolated or formed groups with less than two loci. The thirteen remaining loci were located at three regions in linkage groups Pv04, Pv09, and Pv11. The involvement of Pv09 was discarded due to the observed segregation in the subpopulation obtained from the Xana genotype for the loci located in this region. In contrast, the two subpopulations obtained from the Xana genotype for the BM161 locus, linked to the Co-3/9 anthracnose resistance gene (Pv04), and from the Xana genotype for the SCAReoli locus, linked to the Co-2 anthracnose resistance gene (Pv11), exhibited monogenic segregations, suggesting that both regions were involved in the genetic control of resistance. A genetic dissection was carried out to verify the involvement of both regions in the reaction to PM. Two resistant recombinant lines were selected, according to their genotypes, for the block of loci included in the Co-2 and Co-3/9 regions, and they were crossed with the susceptible parent, Xana. Linkage analysis in the respective F2 populations supported the hypothesis that a dominant gene (Pm1) was located in the linkage group Pv11 and another gene (Pm2) was located in the linkage group Pv04. This is the first report showing the localization of resistance genes against powdery mildew in Phaseolus vulgaris and the results offer the opportunity to increase the efficiency of breeding

  9. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

  10. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants

    Science.gov (United States)

    Gala, Manish; Abecasis, Goncalo; Bezieau, Stephane; Brenner, Hermann; Butterbach, Katja; Caan, Bette J.; Carlson, Christopher S.; Casey, Graham; Chang-Claude, Jenny; Conti, David V.; Curtis, Keith R.; Duggan, David; Gallinger, Steven; Haile, Robert W.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hudson, Thomas J.; Jenkins, Mark A.; Küry, Sébastien; Le Marchand, Loic; Leal, Suzanne M.; Newcomb, Polly A.; Nickerson, Deborah A.; Potter, John D.; Schoen, Robert E.; Schumacher, Fredrick R.; Seminara, Daniela; Slattery, Martha L.; Hsu, Li; Chan, Andrew T.; White, Emily; Berndt, Sonja I.; Peters, Ulrike

    2016-01-01

    Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s). PMID:27379672

  11. Genetic Improvement of Biological Nitrogen Fixation in Common Bean Genotypes (Phaseolus vulgaris L.

    Directory of Open Access Journals (Sweden)

    Ahmad Reza Golparvar

    2012-06-01

    Full Text Available Fifty common bean genotypes were cultivated in two separately field trials at the research station of Islamic Azad University, Khorasgan Branch during 2008-2009. The experimental design was randomized complete block. Bean seeds were inoculated by Rhizobium legominosarum biovar Phaseoli isolate L-109 in one of the experiments before sowing. The dose of Rhizobium for seed inoculation was 7 miligrams of bacteria for 1 kilogram of seed. The second experiment was control. The second experiment was analyzed in the same way as the first except for biological nitrogen fixation. The results showed definite positive and significant correlation in percentage of nitrogen fixation with some other been characters. Step-wise regression designated that total nitrogen percentage in shoot, number of nodules per plant and biomass yield accounted for 93.8% of variation expect for nitrogen fixation percent. Path analysis indicated that total nitrogen percentage in shoot, number of nodules per plant and biomass yield have direct and positive effect on nitrogen fixation index. Hence, total nitrogen percentage in shoot, number of nodules per plant and biomass yield are promising indirect selection criteria for genetic improvement of nitrogen fixation capability in common bean genotypes.

  12. Comparative analysis of phenotypes features in two common genetic variants of limb-girdle muscular dystrophy

    Directory of Open Access Journals (Sweden)

    I. V. Sharkova

    2015-01-01

    Full Text Available The algorithm of differential diagnosis of the two most common genetic variants the limb-girdle muscular dystrophy (LGMD2A and DMD, developed on the basis of a comprehensive survey of 85 patients with a diagnosis specification using techniques of DNA analysis. It is shown that the accurate diagnosis of LGMD genetic types should be based on the results of the clinical and genealogical, biochemical and molecular genetic analysis. The proposed algorithm will significantly reduces the economic and time costs with expensive DNA testing.

  13. Common Control by Compound Samples in Conditional Discriminations

    Science.gov (United States)

    Perez-Gonzalez, Luis Antonio; Alonso-Alvarez, Benigno

    2008-01-01

    We tested whether teaching control by single stimulus samples in conditional discriminations would result in common control of two-stimuli compound samples, and vice versa. In Experiment 1, 5 participants were first taught four single-sample conditional discriminations. The first conditional discrimination was as follows: given sample stimulus P1,…

  14. The relationship between the genetic and environmental influences on common externalizing psychopathology and mental wellbeing.

    Science.gov (United States)

    Kendler, Kenneth S; Myers, John M; Keyes, Corey L M

    2011-12-01

    To determine the relationship between the genetic and environmental risk factors for externalizing psychopathology and mental wellbeing, we examined detailed measures of emotional, social and psychological wellbeing, and a history of alcohol-related problems and smoking behavior in the last year in 1,386 individual twins from same-sex pairs from the MIDUS national US sample assessed in 1995. Cholesky decomposition analyses were performed withthe Mx program. The best fit model contained one highly heritable common externalizing psychopathology factor for both substance use/abuse measures, and one strongly heritable common factor for the three wellbeing measures. Genetic and environmental risk factors for externalizing psychopathology were both negatively associated with levels of mental wellbeing and accounted for, respectively, 7% and 21% of its genetic and environmental influences. Adding internalizing psychopathology assessed in the last year to the model, genetic risk factors unique for externalizing psychopathology were now positively related to levels of mental wellbeing, although accounting for only 5% of the genetic variance. Environmental risk factors unique to externalizing psychopathology continued to be negatively associated with mental wellbeing, accounting for 26% of the environmental variance. When both internalizing psychopathology and externalizing psychopathology are associated with mental wellbeing, the strongest risk factors for low mental wellbeing are genetic factors that impact on both internalizing psychopathology and externalizing psychopathology, and environmental factors unique to externalizing psychopathology. In this model, genetic risk factors for externalizing psychopathology predict, albeit weakly, higher levels of mental wellbeing.

  15. Modeling resistance to genetic control of insects.

    Science.gov (United States)

    Alphey, Nina; Bonsall, Michael B; Alphey, Luke

    2011-02-07

    The sterile insect technique is an area-wide pest control method that reduces pest populations by releasing mass-reared sterile insects which compete for mates with wild insects. Modern molecular tools have created possibilities for improving and extending the sterile insect technique. As with any new insect control method, questions arise about potential resistance. Genetic RIDL(®)(1) (Release of Insects carrying a Dominant Lethal) technology is a proposed modification of the technique, releasing insects that are homozygous for a repressible dominant lethal genetic construct rather than being sterilized by irradiation. Hypothetical resistance to the lethal mechanism is a potential threat to RIDL strategies' effectiveness. Using population genetic and population dynamic models, we assess the circumstances under which monogenic biochemically based resistance could have a significant impact on the effectiveness of releases for population control. We assume that released insects would be homozygous susceptible to the lethal genetic construct and therefore releases would have a built-in element of resistance dilution. We find that this effect could prevent or limit the spread of resistance to RIDL constructs; the outcomes are subject to competing selective forces deriving from the fitness properties of resistance and the release ratio. Resistance that is spreading and capable of having a significant detrimental impact on population reduction is identifiable, signaling in advance a need for mitigating action.

  16. 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

  17. 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

  18. Considering causal genes in the genetic dissection of kernel traits in common wheat.

    Science.gov (United States)

    Mohler, Volker; Albrecht, Theresa; Castell, Adelheid; Diethelm, Manuela; Schweizer, Günther; Hartl, Lorenz

    2016-11-01

    Genetic factors controlling thousand-kernel weight (TKW) were characterized for their association with other seed traits, including kernel width, kernel length, ratio of kernel width to kernel length (KW/KL), kernel area, and spike number per m(2) (SN). For this purpose, a genetic map was established utilizing a doubled haploid population derived from a cross between German winter wheat cultivars Pamier and Format. Association studies in a diversity panel of elite cultivars supplemented genetic analysis of kernel traits. In both populations, genomic signatures of 13 candidate genes for TKW and kernel size were analyzed. Major quantitative trait loci (QTL) for TKW were identified on chromosomes 1B, 2A, 2D, and 4D, and their locations coincided with major QTL for kernel size traits, supporting the common belief that TKW is a function of other kernel traits. The QTL on chromosome 2A was associated with TKW candidate gene TaCwi-A1 and the QTL on chromosome 4D was associated with dwarfing gene Rht-D1. A minor QTL for TKW on chromosome 6B coincided with TaGW2-6B. The QTL for kernel dimensions that did not affect TKW were detected on eight chromosomes. A major QTL for KW/KL located at the distal tip of chromosome arm 5AS is being reported for the first time. TaSus1-7A and TaSAP-A1, closely linked to each other on chromosome 7A, could be related to a minor QTL for KW/KL. Genetic analysis of SN confirmed its negative correlation with TKW in this cross. In the diversity panel, TaSus1-7A was associated with TKW. Compared to the Pamier/Format bi-parental population where TaCwi-A1a was associated with higher TKW, the same allele reduced grain yield in the diversity panel, suggesting opposite effects of TaCwi-A1 on these two traits.

  19. Seewis virus, a genetically distinct hantavirus in the Eurasian common shrew (Sorex araneus

    Directory of Open Access Journals (Sweden)

    Hilbe Monika

    2007-10-01

    Full Text Available Abstract More than 20 years ago, hantaviral antigens were reported in tissues of the Eurasian common shrew (Sorex araneus, Eurasian water shrew (Neomys fodiens and common mole (Talpa europea, suggesting that insectivores, or soricomorphs, might serve as reservoirs of unique hantaviruses. Using RT-PCR, sequences of a genetically distinct hantavirus, designated Seewis virus (SWSV, were amplified from lung tissue of a Eurasian common shrew, captured in October 2006 in Graubünden, Switzerland. Pair-wise analysis of the full-length S and partial M and L segments of SWSV indicated approximately 55%–72% similarity with hantaviruses harbored by Murinae, Arvicolinae, Neotominae and Sigmodontinae rodents. Phylogenetically, SWSV grouped with other recently identified shrew-borne hantaviruses. Intensified efforts are underway to clarify the genetic diversity of SWSV throughout the geographic range of the Eurasian common shrew, as well as to determine its relevance to human health.

  20. Ancient Humans Influenced the Current Spatial Genetic Structure of Common Walnut Populations in Asia.

    Directory of Open Access Journals (Sweden)

    Paola Pollegioni

    Full Text Available Common walnut (Juglans regia L is an economically important species cultivated worldwide for its wood and nuts. It is generally accepted that J. regia survived and grew spontaneously in almost completely isolated stands in its Asian native range after the Last Glacial Maximum. Despite its natural geographic isolation, J. regia evolved over many centuries under the influence of human management and exploitation. We evaluated the hypothesis that the current distribution of natural genetic resources of common walnut in Asia is, at least in part, the product of ancient anthropogenic dispersal, human cultural interactions, and afforestation. Genetic analysis combined with ethno-linguistic and historical data indicated that ancient trade routes such as the Persian Royal Road and Silk Road enabled long-distance dispersal of J. regia from Iran and Trans-Caucasus to Central Asia, and from Western to Eastern China. Ancient commerce also disrupted the local spatial genetic structure of autochthonous walnut populations between Tashkent and Samarkand (Central-Eastern Uzbekistan, where the northern and central routes of the Northern Silk Road converged. A significant association between ancient language phyla and the genetic structure of walnut populations is reported even after adjustment for geographic distances that could have affected both walnut gene flow and human commerce over the centuries. Beyond the economic importance of common walnut, our study delineates an alternative approach for understanding how the genetic resources of long-lived perennial tree species may be affected by the interaction of geography and human history.

  1. Genetic control of leaf curl in maize.

    Science.gov (United States)

    Entringer, G C; Guedes, F L; Oliveira, A A; Nascimento, J P; Souza, J C

    2014-03-17

    Among the many implications of climatic change on agriculture, drought is expected to continue to have a major impact on agribusinesses. Leaf curling is an anatomical characteristic that might be potentially used to enhance plant tolerance to water deficit. Hence, we aimed to study the genetic control of leaf curl in maize. From 2 contrasting inbred lines for the trait, generations F1, F2, and the backcrosses were obtained. All of these generations were evaluated in a randomized block design with 2 replicates. Leaf curl samples were collected from 3 leaves above the first ear at the tasseling stage, and quantified by dividing the width of the leaf blade with natural curling against its extended width. The mean and variance components were estimated by the weighted least square method. It was found that the trait studied has predominance of the additive effects, with genetic control being attributed to few genes that favor selection and exhibit minimal influence from the environment.

  2. Study of the common genetic background for rheumatoid arthritis and systemic lupus erythematosus

    Science.gov (United States)

    Orozco, Gisela; Eyre, Steve; Hinks, Anne; Bowes, John; Morgan, Ann W; Wilson, Anthony G; Wordsworth, Paul; Steer, Sophia; Hocking, Lynne; Thomson, Wendy; Worthington, Jane; Barton, Anne

    2011-01-01

    Background Evidence is beginning to emerge that there may be susceptibility loci for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) that are common to both diseases. Objective To investigate single nucleotide polymorphisms that have been reported to be associated with SLE in a UK cohort of patients with RA and controls. Methods 3962 patients with RA and 9275 controls were included in the study. Eleven SNPs mapping to confirmed SLE loci were investigated. These mapped to the TNFSF4, BANK1, TNIP1, PTTG1, UHRF1BP1, ATG5, JAZF1, BLK, KIAA1542, ITGAM and UBE2L3 loci. Genotype frequencies were compared between patients with RA and controls using the trend test. Results The SNPs mapping to the BLK and UBE2L3 loci showed significant evidence for association with RA. Two other SNPs, mapping to ATG5 and KIAA1542, showed nominal evidence for association with RA (p=0.02 and p=0.02, respectively) but these were not significant after applying a Bonferroni correction. Additionally, a significant global enrichment in carriage of SLE alleles in patients with RA compared with controls (p=9.1×10−7) was found. Meta-analysis of this and previous studies confirmed the association of the BLK and UBE2L3 gene with RA at genome-wide significance levels (p<5×10−8). Together, the authors estimate that the SLE and RA overlapping loci, excluding HLA-DRB1 alleles, identified so far explain ∼5.8% of the genetic susceptibility to RA as a whole. Conclusion The findings confirm the association of the BLK and UBE2L3 loci with RA, thus adding to the list of loci showing overlap between RA and SLE. PMID:21068098

  3. Complete loss of MHC genetic diversity in the Common Hamster (Cricetus cricetus ) population in The Netherlands

    NARCIS (Netherlands)

    Smulders, M.J.M.; Snoek, L.B.; Booy, G.; Vosman, B.

    2003-01-01

    The Common Hamster (Cricetus cricetus L.) has suffered from changes in agricultural practices. In some Western European countries the populations have become so small and scattered that they are threatened with extinction. We studied the genetic diversity of mitochondrial and major histoincompatibil

  4. Prediction of breast cancer risk based on profiling with common genetic variants

    NARCIS (Netherlands)

    N. Mavaddat (Nasim); P.D.P. Pharoah (Paul); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); M.N. Brook (Mark N.); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); A.M. Dunning (Alison); M. Shah (Mitul); R.N. Luben (Robert); J. Brown (Judith); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune F.); H. Flyger (Henrik); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); J. Peto (Julian); I. dos Santos Silva (Isabel); F. Dudbridge (Frank); N. Johnson (Nichola); M.K. Schmidt (Marjanka); A. Broeks (Annegien); S. Verhoef; E.J. Rutgers (Emiel J.); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); L.A. Brinton (Louise); J. Lissowska (Jolanta); F.J. Couch (Fergus); J.E. Olson (Janet); C. Vachon (Celine); V.S. Pankratz (Shane); D. Lambrechts (Diether); H. Wildiers (Hans); C. van Ongeval (Chantal); E. van Limbergen (Erik); V. Kristensen (Vessela); G. Grenaker Alnæs (Grethe); S. Nord (Silje); A.-L. Borresen-Dale (Anne-Lise); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias); B. Burwinkel (Barbara); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); A. Trentham-Dietz (Amy); P. Newcomb (Polly); L. Titus (Linda); K.M. Egan (Kathleen M.); D. Hunter (David); S. Lindstrom (Stephen); R. Tamimi (Rulla); P. Kraft (Peter); N. Rahman (Nazneen); C. Turnbull (Clare); A. Renwick (Anthony); S. Seal (Sheila); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); P. Menéndez (Primitiva); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); T. Dörk (Thilo); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); A. Ziogas (Argyrios); L. Bernstein (Leslie); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); E.K. Khusnutdinova (Elza); M. Bermisheva (Marina); D. Prokofyeva (Darya); Z. Takhirova (Zalina); A. Meindl (Alfons); R.K. Schmutzler (Rita); C. Sutter (Christian); R. Yang (Rongxi); P. Schürmann (Peter); M. Bremer (Michael); H. Christiansen (Hans); T.-W. Park-Simon; P. Hillemanns (Peter); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); M. Sanchez (Marie); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); V. Pensotti (Valeria); J. Hopper (John); H. Tsimiklis (Helen); C. Apicella (Carmel); M.C. Southey (Melissa); H. Brauch (Hiltrud); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun); A.J. Sigurdson (Alice); M.M. Doody (Michele M.); U. Hamann (Ute); D. Torres (Diana); H.U. Ulmer (Hans); A. Försti (Asta); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A. Marie Mulligan (Anna); G. Chenevix-Trench (Georgia); R. Balleine (Rosemary); G.G. Giles (Graham); R.L. Milne (Roger); C.A. McLean (Catriona Ann); A. Lindblom (Annika); S. Margolin (Sara); C.A. Haiman (Christopher); B.E. Henderson (Brian); F. Schumacher (Fredrick); L. Le Marchand (Loic); U. Eilber (Ursula); S. Wang-Gohrke (Shan); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. van den Ouweland (Ans); L.B. Koppert (Linetta); J. Carpenter (Jane); C. Clarke (Christine); R.J. Scott (Rodney J.); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); H. Brenner (Hermann); V. Arndt (Volker); C. Stegmaier (Christa); A. Karina Dieffenbach (Aida); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); K. Offit (Kenneth); J. Vijai (Joseph); M. Robson (Mark); R. Rau-Murthy (Rohini); M. Dwek (Miriam); R. Swann (Ruth); K. Annie Perkins (Katherine); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); D. Eccles (Diana); W. Tapper (William); M. Rafiq (Meena); E.M. John (Esther M.); A.S. Whittemore (Alice); S. Slager (Susan); D. Yannoukakos (Drakoulis); A.E. Toland (Amanda); S. Yao (Song); W. Zheng (Wei); S.L. Halverson (Sandra L.); A. González-Neira (Anna); G. Pita (G.); M. Rosario Alonso; N. Álvarez (Nuria); D. Herrero (Daniel); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); M. Maranian (Melanie); S. Healey (Sue); J. Simard (Jacques); P. Hall (Per); D.F. Easton (Douglas); M. García-Closas (Montserrat)

    2015-01-01

    textabstractBackground: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is l

  5. Neuroinformatic analyses of common and distinct genetic components associated with major neuropsychiatric disorders

    OpenAIRE

    Lotan, Amit; Fenckova, Michaela; Bralten, Janita; Alttoa, Aet; Dixson, Luanna; Williams, Robert W.; van der Voet, Monique

    2014-01-01

    Major neuropsychiatric disorders are highly heritable, with mounting evidence suggesting that these disorders share overlapping sets of molecular and cellular underpinnings. In the current article we systematically test the degree of genetic commonality across six major neuropsychiatric disorders—attention deficit hyperactivity disorder (ADHD), anxiety disorders (Anx), autistic spectrum disorders (ASD), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). We curate...

  6. Common genetic variants and modification of penetrance of BRCA2-associated breast cancer

    DEFF Research Database (Denmark)

    Gaudet, Mia M; Kirchhoff, Tomas; Green, Todd

    2010-01-01

    The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carri...

  7. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

    NARCIS (Netherlands)

    C.A. Rietveld (Niels); T. Esko (Tõnu); G. Davies (Gail); T.H. Pers (Tune); P. Turley (Patrick); B. Benyamin (Beben); C.F. Chabris (Christopher F.); V. Emilsson (Valur); A.D. Johnson (Andrew); J.J. Lee (James J.); C. de Leeuw (Christiaan); R.E. Marioni (Riccardo); S.E. Medland (Sarah Elizabeth); M. Miller (Mike); O. Rostapshova (Olga); S. van der Lee (Sven); A.A.E. Vinkhuyzen (Anna A.); N. Amin (Najaf); D. Conley (Dalton); J. Derringer; C.M. van Duijn (Cock); R.S.N. Fehrmann (Rudolf); L. Franke (Lude); E.L. Glaeser (Edward L.); N.K. Hansell (Narelle); C. Hayward (Caroline); W.G. Iacono (William); C.A. Ibrahim-Verbaas (Carla); V.W.V. Jaddoe (Vincent); J. Karjalainen (Juha); D. Laibson (David); P. Lichtenstein (Paul); D.C. Liewald (David C.); P.K. Magnusson (Patrik); N.G. Martin (Nicholas); M. McGue (Matt); G. Mcmahon (George); N.L. Pedersen (Nancy); S. Pinker (Steven); D.J. Porteous (David J.); D. Posthuma (Danielle); F. Rivadeneira Ramirez (Fernando); B.H. Smithk (Blair H.); J.M. Starr (John); H.W. Tiemeier (Henning); N.J. Timpsonm (Nicholas J.); M. Trzaskowskin (Maciej); A.G. Uitterlinden (André); F.C. Verhulst (Frank); M.E. Ward (Mary); M.J. Wright (Margaret); G.D. Smith; I.J. Deary (Ian J.); M. Johannesson (Magnus); R. Plomin (Robert); P.M. Visscher (Peter); D.J. Benjamin (Daniel J.); D. Cesarini (David); Ph.D. Koellinger (Philipp)

    2014-01-01

    textabstractWe identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxyphenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education

  8. Common genetic variants and modification of penetrance of BRCA2-associated breast cancer

    NARCIS (Netherlands)

    M.M. Gaudet (Mia); T. Kircchoff (Tomas); T. Green (Todd); J. Vijai (Joseph); J.M. Korn (Joshua); C. Guiducci (Candace); A.V. Segrè (Ayellet); K. McGee (Kate); L. McGuffog (Lesley); C. Kartsonaki (Christiana); J. Morrison (Jonathan); S. Healey (Sue); O. Sinilnikova (Olga); D. Stoppa-Lyonnet (Dominique); S. Mazoyer (Sylvie); M. Gauthier-Villars (Marion); H. Sobol (Hagay); M. Longy (Michel); M. Frenay (Marc); F.B.L. Hogervorst (Frans); M.A. Rookus (Matti); J.M. Collée (Margriet); N. Hoogerbrugge (Nicoline); K.E. van Roozendaal (Kees); M. Piedemonte (Marion); W.S. Rubinstein (Wendy); S. Nerenstone (Stacy); L. van Le (Linda); S.V. Blank (Stephanie); T. Caldes (Trinidad); M. de La Hoya (Miguel); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); C. Lazaro (Conxi); I. Blanco (Ignacio); A. Arason (Adalgeir); O.T. Johannson (Oskar); R.B. Barkardottir (Rosa); P. Devilee (Peter); O.I. Olopade (Olofunmilayo); S.L. Neuhausen (Susan); X. Wang (Xianshu); Z. Fredericksen (Zachary); P. Peterlongo (Paolo); S. Manoukian (Siranoush); M. Barile (Monica); A. Viel (Alessandra); P. Radice (Paolo); C. Phelan (Catherine); S. Narod (Steven); G. Rennert (Gad); F. Lejbkowicz (Flavio); A. Flugelman (Anath); I.L. Andrulis (Irene); G. Glendon (Gord); H. Ozcelik (Hilmi); A.E. Toland (Amanda); M. Montagna (Marco); E. D'Andrea (Emma); E. Friedman (Eitan); Y. Laitman (Yael); Å. Borg (Åke); M.S. Beattie (Mary); S.J. Ramus (Susan); S.M. Domchek (Susan); K.L. Nathanson (Katherine); R. Rebbeck (Timothy); A.B. Spurdle (Amanda); X. Chen (Xiaoqing); H. Holland (Helene); E.M. John (Esther); J. Hopper (John); S.S. Buys (Saundra); M.B. Daly (Mary); M.C. Southey (Melissa); M-B. Terry (Mary-beth); N. Tung (Nadine); T.V.O. Hansen (Thomas); F.C. Nielsen (Finn); M.H. Greene (Mark); P.L. Mai (Phuong); A. Osorio (Ana); M. Duran; R. Andres (Raquel); J. Benítez (Javier); J.N. Weitzel (Jeffrey); J. Garber (Judy); U. Hamann (Ute); S. Peock (Susan); M. Cook (Margaret); C.T. Oliver (Clare); D. Frost (Debra); R. Platte (Radka); D.G. Evans (Gareth); F. Lalloo (Fiona); R. Eeles (Rosalind); L. Izatt (Louise); L.J. Walker (Lisa); J. Eason (Jacqueline); J. Barwell (Julian); A.K. Godwin (Andrew); R.K. Schmutzler (Rita); B. Wapenschmidt (Barbara); S. Engert (Stefanie); N. Arnold (Norbert); D. Gadzicki (Dorothea); M. Dean (Michael Emmans); B. Gold (Bert); R.J. Klein (Robert); F.J. Couch (Fergus); G. Chenevix-Trench (Georgia); D.F. Easton (Douglas); M.J. Daly (Mark); A.C. Antoniou (Antonis); D. Altshuler (David); K. Offit (Kenneth)

    2010-01-01

    textabstractThe considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2

  9. Common genetic variants and modification of penetrance of BRCA2-associated breast cancer

    NARCIS (Netherlands)

    M.M. Gaudet (Mia); T. Kircchoff (Tomas); T. Green (Todd); J. Vijai (Joseph); J.M. Korn (Joshua); C. Guiducci (Candace); A.V. Segrè (Ayellet); K. McGee (Kate); L. McGuffog (Lesley); C. Kartsonaki (Christiana); J. Morrison (Jonathan); S. Healey (Sue); O. Sinilnikova (Olga); D. Stoppa-Lyonnet (Dominique); S. Mazoyer (Sylvie); M. Gauthier-Villars (Marion); H. Sobol (Hagay); M. Longy (Michel); M. Frenay (Marc); F.B.L. Hogervorst (Frans); M.A. Rookus (Matti); J.M. Collée (Margriet); N. Hoogerbrugge (Nicoline); K.E. van Roozendaal (Kees); M. Piedemonte (Marion); W.S. Rubinstein (Wendy); S. Nerenstone (Stacy); L. van Le (Linda); S.V. Blank (Stephanie); T. Caldes (Trinidad); M. de La Hoya (Miguel); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); C. Lazaro (Conxi); I. Blanco (Ignacio); A. Arason (Adalgeir); O.T. Johannson (Oskar); R.B. Barkardottir (Rosa); P. Devilee (Peter); O.I. Olopade (Olofunmilayo); S.L. Neuhausen (Susan); X. Wang (Xianshu); Z. Fredericksen (Zachary); P. Peterlongo (Paolo); S. Manoukian (Siranoush); M. Barile (Monica); A. Viel (Alessandra); P. Radice (Paolo); C. Phelan (Catherine); S. Narod (Steven); G. Rennert (Gad); F. Lejbkowicz (Flavio); A. Flugelman (Anath); I.L. Andrulis (Irene); G. Glendon (Gord); H. Ozcelik (Hilmi); A.E. Toland (Amanda); M. Montagna (Marco); E. D'Andrea (Emma); E. Friedman (Eitan); Y. Laitman (Yael); Å. Borg (Åke); M.S. Beattie (Mary); S.J. Ramus (Susan); S.M. Domchek (Susan); K.L. Nathanson (Katherine); R. Rebbeck (Timothy); A.B. Spurdle (Amanda); X. Chen (Xiaoqing); H. Holland (Helene); E.M. John (Esther); J. Hopper (John); S.S. Buys (Saundra); M.B. Daly (Mary); M.C. Southey (Melissa); M-B. Terry (Mary-beth); N. Tung (Nadine); T.V.O. Hansen (Thomas); F.C. Nielsen (Finn); M.H. Greene (Mark); P.L. Mai (Phuong); A. Osorio (Ana); M. Duran; R. Andres (Raquel); J. Benítez (Javier); J.N. Weitzel (Jeffrey); J. Garber (Judy); U. Hamann (Ute); S. Peock (Susan); M. Cook (Margaret); C.T. Oliver (Clare); D. Frost (Debra); R. Platte (Radka); D.G. Evans (Gareth); F. Lalloo (Fiona); R. Eeles (Rosalind); L. Izatt (Louise); L.J. Walker (Lisa); J. Eason (Jacqueline); J. Barwell (Julian); A.K. Godwin (Andrew); R.K. Schmutzler (Rita); B. Wapenschmidt (Barbara); S. Engert (Stefanie); N. Arnold (Norbert); D. Gadzicki (Dorothea); M. Dean (Michael Emmans); B. Gold (Bert); R.J. Klein (Robert); F.J. Couch (Fergus); G. Chenevix-Trench (Georgia); D.F. Easton (Douglas); M.J. Daly (Mark); A.C. Antoniou (Antonis); D. Altshuler (David); K. Offit (Kenneth)

    2010-01-01

    textabstractThe considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutat

  10. Prediction of breast cancer risk based on profiling with common genetic variants

    NARCIS (Netherlands)

    N. Mavaddat (Nasim); P.D.P. Pharoah (Paul); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); M.N. Brook (Mark N.); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); A.M. Dunning (Alison); M. Shah (Mitul); R.N. Luben (Robert); J. Brown (Judith); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune F.); H. Flyger (Henrik); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); J. Peto (Julian); I. dos Santos Silva (Isabel); F. Dudbridge (Frank); N. Johnson (Nichola); M.K. Schmidt (Marjanka); A. Broeks (Annegien); S. Verhoef; E.J. Rutgers (Emiel J.); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); L.A. Brinton (Louise); J. Lissowska (Jolanta); F.J. Couch (Fergus); J.E. Olson (Janet); C. Vachon (Celine); V.S. Pankratz (Shane); D. Lambrechts (Diether); H. Wildiers (Hans); C. van Ongeval (Chantal); E. van Limbergen (Erik); V. Kristensen (Vessela); G. Grenaker Alnæs (Grethe); S. Nord (Silje); A.-L. Borresen-Dale (Anne-Lise); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias); B. Burwinkel (Barbara); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); A. Trentham-Dietz (Amy); P. Newcomb (Polly); L. Titus (Linda); K.M. Egan (Kathleen M.); D. Hunter (David); S. Lindstrom (Stephen); R. Tamimi (Rulla); P. Kraft (Peter); N. Rahman (Nazneen); C. Turnbull (Clare); A. Renwick (Anthony); S. Seal (Sheila); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); P. Menéndez (Primitiva); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); T. Dörk (Thilo); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); A. Ziogas (Argyrios); L. Bernstein (Leslie); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); E.K. Khusnutdinova (Elza); M. Bermisheva (Marina); D. Prokofyeva (Darya); Z. Takhirova (Zalina); A. Meindl (Alfons); R.K. Schmutzler (Rita); C. Sutter (Christian); R. Yang (Rongxi); P. Schürmann (Peter); M. Bremer (Michael); H. Christiansen (Hans); T.-W. Park-Simon; P. Hillemanns (Peter); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); M. Sanchez (Marie); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); V. Pensotti (Valeria); J. Hopper (John); H. Tsimiklis (Helen); C. Apicella (Carmel); M.C. Southey (Melissa); H. Brauch (Hiltrud); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun); A.J. Sigurdson (Alice); M.M. Doody (Michele M.); U. Hamann (Ute); D. Torres (Diana); H.U. Ulmer (Hans); A. Försti (Asta); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A. Marie Mulligan (Anna); G. Chenevix-Trench (Georgia); R. Balleine (Rosemary); G.G. Giles (Graham); R.L. Milne (Roger); C.A. McLean (Catriona Ann); A. Lindblom (Annika); S. Margolin (Sara); C.A. Haiman (Christopher); B.E. Henderson (Brian); F. Schumacher (Fredrick); L. Le Marchand (Loic); U. Eilber (Ursula); S. Wang-Gohrke (Shan); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. van den Ouweland (Ans); L.B. Koppert (Lisa); J. Carpenter (Jane); C. Clarke (Christine); R.J. Scott (Rodney J.); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); H. Brenner (Hermann); V. Arndt (Volker); C. Stegmaier (Christa); A. Karina Dieffenbach (Aida); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); K. Offit (Kenneth); J. Vijai (Joseph); M. Robson (Mark); R. Rau-Murthy (Rohini); M. Dwek (Miriam); R. Swann (Ruth); K. Annie Perkins (Katherine); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); D. Eccles (Diana); W. Tapper (William); M. Rafiq (Meena); E.M. John (Esther M.); A.S. Whittemore (Alice); S. Slager (Susan); D. Yannoukakos (Drakoulis); A.E. Toland (Amanda); S. Yao (Song); W. Zheng (Wei); S.L. Halverson (Sandra L.); A. González-Neira (Anna); G. Pita (G.); M. Rosario Alonso; N. Álvarez (Nuria); D. Herrero (Daniel); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); M. Maranian (Melanie); S. Healey (Sue); J. Simard (Jacques); P. Hall (Per); D.F. Easton (Douglas); M. García-Closas (Montserrat)

    2015-01-01

    textabstractBackground: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is l

  11. Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer

    NARCIS (Netherlands)

    Gaudet, Mia M.; Kirchhoff, Tomas; Green, Todd; Vijai, Joseph; Korn, Joshua M.; Guiducci, Candace; Segre, Ayellet V.; McGee, Kate; McGuffog, Lesley; Kartsonaki, Christiana; Morrison, Jonathan; Healey, Sue; Sinilnikova, Olga M.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Gauthier-Villars, Marion; Sobol, Hagay; Longy, Michel; Frenay, Marc; Hogervorst, Frans B. L.; Rookus, Matti A.; Collee, J. Margriet; Hoogerbrugge, Nicoline; van Roozendaal, Kees E. P.; Piedmonte, Marion; Rubinstein, Wendy; Nerenstone, Stacy; Van Le, Linda; Blank, Stephanie V.; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomaki, Kristiina; Lazaro, Conxi; Blanco, Ignacio; Arason, Adalgeir; Johannsson, Oskar T.; Barkardottir, Rosa B.; Devilee, Peter; Olopade, Olofunmilayo I.; Neuhausen, Susan L.; Wang, Xianshu; Fredericksen, Zachary S.; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Viel, Alessandra; Radice, Paolo; Phelan, Catherine M.; Narod, Steven; Rennert, Gad; Lejbkowicz, Flavio; Flugelman, Anath; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Toland, Amanda E.; Montagna, Marco; D'Andrea, Emma; Friedman, Eitan; Laitman, Yael; Borg, Ake; Beattie, Mary; Ramus, Susan J.; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Tim; Spurdle, Amanda B.; Chen, Xiaoqing; Holland, Helene; John, Esther M.; Hopper, John L.; Buys, Saundra S.; Daly, Mary B.; Southey, Melissa C.; Terry, Mary Beth; Tung, Nadine; Hansen, Thomas V. Overeem; Nielsen, Finn C.; Greene, Mark I.; Mai, Phuong L.; Osorio, Ana; Duran, Mercedes; Andres, Raquel; Benitez, Javier; Weitzel, Jeffrey N.; Garber, Judy; Hamann, Ute; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Platte, Radka; Evans, D. Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Walker, Lisa; Eason, Jacqueline; Barwell, Julian; Godwin, Andrew K.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engert, Stefanie; Arnold, Norbert; Gadzicki, Dorothea; Dean, Michael; Gold, Bert; Klein, Robert J.; Couch, Fergus J.; Chenevix-Trench, Georgia; Easton, Douglas F.; Daly, Mark J.; Antoniou, Antonis C.; Altshuler, David M.; Offit, Kenneth

    2010-01-01

    The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers

  12. Common Genetic and Environmental Influences on Major Depressive Disorder and Conduct Disorder

    Science.gov (United States)

    Subbarao, Anjali; Rhee, Soo Hyun; Young, Susan E.; Ehringer, Marissa A.; Corley, Robin P.; Hewitt, John K.

    2008-01-01

    The evidence for common genetic and environmental influences on conduct disorder (CD) and major depressive disorder (MDD) in adolescents was examined. A sample of 570 monozygotic twin pairs, 592 dizygotic twin pairs, and 426 non-twin siblings, aged 12-18 years, was recruited from the Colorado Twin Registry. For the past year data, there was a…

  13. Prediction of breast cancer risk based on profiling with common genetic variants

    NARCIS (Netherlands)

    N. Mavaddat (Nasim); P.D.P. Pharoah (Paul); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); M.N. Brook (Mark N.); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); A.M. Dunning (Alison); M. Shah (Mitul); R.N. Luben (Robert); J. Brown (Judith); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune F.); H. Flyger (Henrik); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); J. Peto (Julian); I. dos Santos Silva (Isabel); F. Dudbridge (Frank); N. Johnson (Nichola); M.K. Schmidt (Marjanka); A. Broeks (Annegien); S. Verhoef; E.J. Rutgers (Emiel J.); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); L.A. Brinton (Louise); J. Lissowska (Jolanta); F.J. Couch (Fergus); J.E. Olson (Janet); C. Vachon (Celine); V.S. Pankratz (Shane); D. Lambrechts (Diether); H. Wildiers (Hans); C. van Ongeval (Chantal); E. van Limbergen (Erik); V. Kristensen (Vessela); G. Grenaker Alnæs (Grethe); S. Nord (Silje); A.-L. Borresen-Dale (Anne-Lise); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias); B. Burwinkel (Barbara); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); A. Trentham-Dietz (Amy); P. Newcomb (Polly); L. Titus (Linda); K.M. Egan (Kathleen M.); D. Hunter (David); S. Lindstrom (Stephen); R. Tamimi (Rulla); P. Kraft (Peter); N. Rahman (Nazneen); C. Turnbull (Clare); A. Renwick (Anthony); S. Seal (Sheila); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); P. Menéndez (Primitiva); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); T. Dörk (Thilo); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); A. Ziogas (Argyrios); L. Bernstein (Leslie); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); E.K. Khusnutdinova (Elza); M. Bermisheva (Marina); D. Prokofyeva (Darya); Z. Takhirova (Zalina); A. Meindl (Alfons); R.K. Schmutzler (Rita); C. Sutter (Christian); R. Yang (Rongxi); P. Schürmann (Peter); M. Bremer (Michael); H. Christiansen (Hans); T.-W. Park-Simon; P. Hillemanns (Peter); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); M. Sanchez (Marie); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); V. Pensotti (Valeria); J. Hopper (John); H. Tsimiklis (Helen); C. Apicella (Carmel); M.C. Southey (Melissa); H. Brauch (Hiltrud); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun); A.J. Sigurdson (Alice); M.M. Doody (Michele M.); U. Hamann (Ute); D. Torres (Diana); H.U. Ulmer (Hans); A. Försti (Asta); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A. Marie Mulligan (Anna); G. Chenevix-Trench (Georgia); R. Balleine (Rosemary); G.G. Giles (Graham); R.L. Milne (Roger); C.A. McLean (Catriona Ann); A. Lindblom (Annika); S. Margolin (Sara); C.A. Haiman (Christopher); B.E. Henderson (Brian); F. Schumacher (Fredrick); L. Le Marchand (Loic); U. Eilber (Ursula); S. Wang-Gohrke (Shan); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. van den Ouweland (Ans); L.B. Koppert (Lisa); J. Carpenter (Jane); C. Clarke (Christine); R.J. Scott (Rodney J.); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); H. Brenner (Hermann); V. Arndt (Volker); C. Stegmaier (Christa); A. Karina Dieffenbach (Aida); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); K. Offit (Kenneth); J. Vijai (Joseph); M. Robson (Mark); R. Rau-Murthy (Rohini); M. Dwek (Miriam); R. Swann (Ruth); K. Annie Perkins (Katherine); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); D. Eccles (Diana); W. Tapper (William); M. Rafiq (Meena); E.M. John (Esther M.); A.S. Whittemore (Alice); S. Slager (Susan); D. Yannoukakos (Drakoulis); A.E. Toland (Amanda); S. Yao (Song); W. Zheng (Wei); S.L. Halverson (Sandra L.); A. González-Neira (Anna); G. Pita (G.); M. Rosario Alonso; N. Álvarez (Nuria); D. Herrero (Daniel); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); M. Maranian (Melanie); S. Healey (Sue); J. Simard (Jacques); P. Hall (Per); D.F. Easton (Douglas); M. García-Closas (Montserrat)

    2015-01-01

    textabstractBackground: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is

  14. Geographical genetic diversity and divergence of common wild rice (O. rufipogon Griff.) in China

    Institute of Scientific and Technical Information of China (English)

    WANG MeiXing; LIChen; LI ZiChao; ZHANG HongLiang; ZHANG DongLing; PAN DaJian; LI DaoYuan; FAN ZhiLan; QI YongWen; SUN JunLi; YANG QingWen

    2008-01-01

    Using 36 SSR markers and 889 accessions of common wild rice in China, the genetic diversity and the divergence among different geographical populations are investigated. Guangdong Province has the largest number of alleles, which account for 84% of the total alleles detected in the study, followed by Guangxi Province. The Nei's gone diversity indices, from high to low, are in the sequence of Hainan, Guangdong, Guangxi, Fujian, Hunan, Jiangxi, and Yunnan provinces. Two genetic diversity centers of Chinese common wild rice are detected on the basis of geographic analysis, i.e., the region covering Boluo, Zijin, Lufeng, Haifeng, Huidong and Huiyang counties of Guangdong Province and the region covering Yongning, Longan, Laibin and Guigang counties of Guangxi Province. The common wild rice in Yunnan, Hunan, Jiangxi, and Fujian provinces are diverged into respectively independent popula-tions with relatively large genetic distances, whereas, those in Hainan, Guangdong and Guangxi prov-inces have relatively low genetic divergence. Under the condition of geographic separation, natural selection is considered as one of the primary forces contributing to the divergence of common wild rice in China.

  15. Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer

    NARCIS (Netherlands)

    Gaudet, Mia M.; Kirchhoff, Tomas; Green, Todd; Vijai, Joseph; Korn, Joshua M.; Guiducci, Candace; Segre, Ayellet V.; McGee, Kate; McGuffog, Lesley; Kartsonaki, Christiana; Morrison, Jonathan; Healey, Sue; Sinilnikova, Olga M.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Gauthier-Villars, Marion; Sobol, Hagay; Longy, Michel; Frenay, Marc; Hogervorst, Frans B. L.; Rookus, Matti A.; Collee, J. Margriet; Hoogerbrugge, Nicoline; van Roozendaal, Kees E. P.; Piedmonte, Marion; Rubinstein, Wendy; Nerenstone, Stacy; Van Le, Linda; Blank, Stephanie V.; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomaki, Kristiina; Lazaro, Conxi; Blanco, Ignacio; Arason, Adalgeir; Johannsson, Oskar T.; Barkardottir, Rosa B.; Devilee, Peter; Olopade, Olofunmilayo I.; Neuhausen, Susan L.; Wang, Xianshu; Fredericksen, Zachary S.; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Viel, Alessandra; Radice, Paolo; Phelan, Catherine M.; Narod, Steven; Rennert, Gad; Lejbkowicz, Flavio; Flugelman, Anath; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Toland, Amanda E.; Montagna, Marco; D'Andrea, Emma; Friedman, Eitan; Laitman, Yael; Borg, Ake; Beattie, Mary; Ramus, Susan J.; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Tim; Spurdle, Amanda B.; Chen, Xiaoqing; Holland, Helene; John, Esther M.; Hopper, John L.; Buys, Saundra S.; Daly, Mary B.; Southey, Melissa C.; Terry, Mary Beth; Tung, Nadine; Hansen, Thomas V. Overeem; Nielsen, Finn C.; Greene, Mark I.; Mai, Phuong L.; Osorio, Ana; Duran, Mercedes; Andres, Raquel; Benitez, Javier; Weitzel, Jeffrey N.; Garber, Judy; Hamann, Ute; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Platte, Radka; Evans, D. Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Walker, Lisa; Eason, Jacqueline; Barwell, Julian; Godwin, Andrew K.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engert, Stefanie; Arnold, Norbert; Gadzicki, Dorothea; Dean, Michael; Gold, Bert; Klein, Robert J.; Couch, Fergus J.; Chenevix-Trench, Georgia; Easton, Douglas F.; Daly, Mark J.; Antoniou, Antonis C.; Altshuler, David M.; Offit, Kenneth

    2010-01-01

    The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers

  16. Common genetic variants and modification of penetrance of BRCA2-associated breast cancer

    NARCIS (Netherlands)

    M.M. Gaudet (Mia); T. Kircchoff (Tomas); T. Green (Todd); J. Vijai (Joseph); J.M. Korn (Joshua); C. Guiducci (Candace); A.V. Segrè (Ayellet); K. McGee (Kate); L. McGuffog (Lesley); C. Kartsonaki (Christiana); J. Morrison (Jonathan); S. Healey (Sue); O. Sinilnikova (Olga); D. Stoppa-Lyonnet (Dominique); S. Mazoyer (Sylvie); M. Gauthier-Villars (Marion); H. Sobol (Hagay); M. Longy (Michel); M. Frenay (Marc); F.B.L. Hogervorst (Frans); M.A. Rookus (Matti); J.M. Collée (Margriet); N. Hoogerbrugge (Nicoline); K.E. van Roozendaal (Kees); M. Piedemonte (Marion); W.S. Rubinstein (Wendy); S. Nerenstone (Stacy); L. van Le (Linda); S.V. Blank (Stephanie); T. Caldes (Trinidad); M. de La Hoya (Miguel); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); C. Lazaro (Conxi); I. Blanco (Ignacio); A. Arason (Adalgeir); O.T. Johannson (Oskar); R.B. Barkardottir (Rosa); P. Devilee (Peter); O.I. Olopade (Olofunmilayo); S.L. Neuhausen (Susan); X. Wang (Xianshu); Z. Fredericksen (Zachary); P. Peterlongo (Paolo); S. Manoukian (Siranoush); M. Barile (Monica); A. Viel (Alessandra); P. Radice (Paolo); C. Phelan (Catherine); S. Narod (Steven); G. Rennert (Gad); F. Lejbkowicz (Flavio); A. Flugelman (Anath); I.L. Andrulis (Irene); G. Glendon (Gord); H. Ozcelik (Hilmi); A.E. Toland (Amanda); M. Montagna (Marco); E. D'Andrea (Emma); E. Friedman (Eitan); Y. Laitman (Yael); Å. Borg (Åke); M.S. Beattie (Mary); S.J. Ramus (Susan); S.M. Domchek (Susan); K.L. Nathanson (Katherine); R. Rebbeck (Timothy); A.B. Spurdle (Amanda); X. Chen (Xiaoqing); H. Holland (Helene); E.M. John (Esther); J. Hopper (John); S.S. Buys (Saundra); M.B. Daly (Mary); M.C. Southey (Melissa); M-B. Terry (Mary-beth); N. Tung (Nadine); T.V.O. Hansen (Thomas); F.C. Nielsen (Finn); M.H. Greene (Mark); P.L. Mai (Phuong); A. Osorio (Ana); M. Duran; R. Andres (Raquel); J. Benítez (Javier); J.N. Weitzel (Jeffrey); J. Garber (Judy); U. Hamann (Ute); S. Peock (Susan); M. Cook (Margaret); C.T. Oliver (Clare); D. Frost (Debra); R. Platte (Radka); D.G. Evans (Gareth); F. Lalloo (Fiona); R. Eeles (Rosalind); L. Izatt (Louise); L.J. Walker (Lisa); J. Eason (Jacqueline); J. Barwell (Julian); A.K. Godwin (Andrew); R.K. Schmutzler (Rita); B. Wapenschmidt (Barbara); S. Engert (Stefanie); N. Arnold (Norbert); D. Gadzicki (Dorothea); M. Dean (Michael Emmans); B. Gold (Bert); R.J. Klein (Robert); F.J. Couch (Fergus); G. Chenevix-Trench (Georgia); D.F. Easton (Douglas); M.J. Daly (Mark); A.C. Antoniou (Antonis); D. Altshuler (David); K. Offit (Kenneth)

    2010-01-01

    textabstractThe considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutat

  17. Common genetic variants and modification of penetrance of BRCA2-associated breast cancer

    DEFF Research Database (Denmark)

    Gaudet, Mia M; Kirchhoff, Tomas; Green, Todd;

    2010-01-01

    The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation...

  18. Effects of common germ-line genetic variation in cell cycle genes on ovarian cancer survival

    DEFF Research Database (Denmark)

    Song, H.; Hogdall, E.; Ramus, S.J.

    2008-01-01

    PURPOSE: Somatic alterations have been shown to correlate with ovarian cancer prognosis and survival, but less is known about the effects on survival of common inherited genetic variation. Of particular interest are genes involved in cell cycle pathways, which regulate cell division and could pla...

  19. Prediction of breast cancer risk based on profiling with common genetic variants

    DEFF Research Database (Denmark)

    Mavaddat, Nasim; Pharoah, Paul D P; Michailidou, Kyriaki

    2015-01-01

    BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. M...

  20. The effects of common genetic variants in oncogenes on ovarian cancer survival

    DEFF Research Database (Denmark)

    Quaye, L.; Gayther, S.A.; Ramus, S.J.

    2008-01-01

    PURPOSE: The 5-year survival rate for invasive epithelial ovarian cancer is <35%. It has been suggested that common, germline genetic variation may influence survival after cancer diagnoses, which might enable the prediction of response to treatment and survival in the clinical setting. The aim o...

  1. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

    NARCIS (Netherlands)

    Rietveld, Cornelius A; Esko, Tõnu; Davies, Gail; Pers, Tune H; Turley, Patrick; Benyamin, Beben; Chabris, Christopher F; Emilsson, Valur; Johnson, Andrew D; Lee, James J; de Leeuw, Christiaan; Marioni, Riccardo E; Medland, Sarah E; Miller, Michael B; Rostapshova, Olga; van der Lee, Sven J; Vinkhuyzen, Anna A E; Amin, Najaf; Conley, Dalton; Derringer, Jaime; van Duijn, Cornelia M; Fehrmann, Rudolf; Franke, Lude; Glaeser, Edward L; Hansell, Narelle K; Hayward, Caroline; Iacono, William G; Ibrahim-Verbaas, Carla; Jaddoe, Vincent; Karjalainen, Juha; Laibson, David; Lichtenstein, Paul; Liewald, David C; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; McMahon, George; Pedersen, Nancy L; Pinker, Steven; Porteous, David J; Posthuma, Danielle; Rivadeneira, Fernando; Smith, Blair H; Starr, John M; Tiemeier, Henning; Timpson, Nicholas J; Trzaskowski, Maciej; Uitterlinden, André G; Verhulst, Frank C; Ward, Mary E; Wright, Margaret J; Davey Smith, George; Deary, Ian J; Johannesson, Magnus; Plomin, Robert; Visscher, Peter M; Benjamin, Daniel J; Cesarini, David; Koellinger, Philipp D

    2014-01-01

    We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated

  2. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

    NARCIS (Netherlands)

    Rietveld, Cornelius A; Esko, Tõnu; Davies, Gail; Pers, Tune H; Turley, Patrick; Benyamin, Beben; Chabris, Christopher F; Emilsson, Valur; Johnson, Andrew D; Lee, James J; de Leeuw, Christiaan; Marioni, Riccardo E; Medland, Sarah E; Miller, Michael B; Rostapshova, Olga; van der Lee, Sven J; Vinkhuyzen, Anna A E; Amin, Najaf; Conley, Dalton; Derringer, Jaime; van Duijn, Cornelia M; Fehrmann, Rudolf; Franke, Lude; Glaeser, Edward L; Hansell, Narelle K; Hayward, Caroline; Iacono, William G; Ibrahim-Verbaas, Carla; Jaddoe, Vincent; Karjalainen, Juha; Laibson, David; Lichtenstein, Paul; Liewald, David C; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; McMahon, George; Pedersen, Nancy L; Pinker, Steven; Porteous, David J; Posthuma, Danielle; Rivadeneira, Fernando; Smith, Blair H; Starr, John M; Tiemeier, Henning; Timpson, Nicholas J; Trzaskowski, Maciej; Uitterlinden, André G; Verhulst, Frank C; Ward, Mary E; Wright, Margaret J; Davey Smith, George; Deary, Ian J; Johannesson, Magnus; Plomin, Robert; Visscher, Peter M; Benjamin, Daniel J; Cesarini, David; Koellinger, Philipp D

    2014-01-01

    We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated

  3. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

    NARCIS (Netherlands)

    C.A. Rietveld (Niels); T. Esko (Tõnu); G. Davies (Gail); T.H. Pers (Tune); P. Turley (Patrick); B. Benyamin (Beben); C.F. Chabris (Christopher F.); V. Emilsson (Valur); A.D. Johnson (Andrew); J.J. Lee (James J.); C. de Leeuw (Christiaan); R.E. Marioni (Riccardo); S.E. Medland (Sarah Elizabeth); M. Miller (Mike); O. Rostapshova (Olga); S. van der Lee (Sven); A.A.E. Vinkhuyzen (Anna A.); N. Amin (Najaf); D. Conley (Dalton); J. Derringer; C.M. van Duijn (Cock); R.S.N. Fehrmann (Rudolf); L. Franke (Lude); E.L. Glaeser (Edward L.); N.K. Hansell (Narelle); C. Hayward (Caroline); W.G. Iacono (William); C.A. Ibrahim-Verbaas (Carla); V.W.V. Jaddoe (Vincent); J. Karjalainen (Juha); D. Laibson (David); P. Lichtenstein (Paul); D.C. Liewald (David C.); P.K. Magnusson (Patrik); N.G. Martin (Nicholas); M. McGue (Matt); G. Mcmahon (George); N.L. Pedersen (Nancy); S. Pinker (Steven); D.J. Porteous (David J.); D. Posthuma (Danielle); F. Rivadeneira Ramirez (Fernando); B.H. Smithk (Blair H.); J.M. Starr (John); H.W. Tiemeier (Henning); N.J. Timpsonm (Nicholas J.); M. Trzaskowskin (Maciej); A.G. Uitterlinden (André); F.C. Verhulst (Frank); M.E. Ward (Mary); M.J. Wright (Margaret); G.D. Smith; I.J. Deary (Ian J.); M. Johannesson (Magnus); R. Plomin (Robert); P.M. Visscher (Peter); D.J. Benjamin (Daniel J.); D. Cesarini (David); Ph.D. Koellinger (Philipp)

    2014-01-01

    textabstractWe identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxyphenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education

  4. Neanderthal and Denisova genetic affinities with contemporary humans: introgression versus common ancestral polymorphisms.

    Science.gov (United States)

    Lowery, Robert K; Uribe, Gabriel; Jimenez, Eric B; Weiss, Mark A; Herrera, Kristian J; Regueiro, Maria; Herrera, Rene J

    2013-11-01

    Analyses of the genetic relationships among modern humans, Neanderthals and Denisovans have suggested that 1-4% of the non-Sub-Saharan African gene pool may be Neanderthal derived, while 6-8% of the Melanesian gene pool may be the product of admixture between the Denisovans and the direct ancestors of Melanesians. In the present study, we analyzed single nucleotide polymorphism (SNP) diversity among a worldwide collection of contemporary human populations with respect to the genetic constitution of these two archaic hominins and Pan troglodytes (chimpanzee). We partitioned SNPs into subsets, including those that are derived in both archaic lineages, those that are ancestral in both archaic lineages and those that are only derived in one archaic lineage. By doing this, we have conducted separate examinations of subsets of mutations with higher probabilities of divergent phylogenetic origins. While previous investigations have excluded SNPs from common ancestors in principal component analyses, we included common ancestral SNPs in our analyses to visualize the relative placement of the Neanderthal and Denisova among human populations. To assess the genetic similarities among the various hominin lineages, we performed genetic structure analyses to provide a comparison of genetic patterns found within contemporary human genomes that may have archaic or common ancestral roots. Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe. Our results suggest that Neanderthal genetic associations with contemporary non-Sub-Saharan African populations, as well as the genetic affinities observed between Denisovans and Melanesians most likely result from the retention of ancient mutations in these populations.

  5. Convergence of circuit dysfunction in ASD: a common bridge between diverse genetic and environmental risk factors and common clinical electrophysiology

    Science.gov (United States)

    Port, Russell G.; Gandal, Michael J.; Roberts, Timothy P. L.; Siegel, Steven J.; Carlson, Gregory C.

    2014-01-01

    Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD). Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents). Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in vivo and ex vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD. PMID:25538564

  6. Convergence of circuit dysfunction in ASD: a common bridge between diverse genetic and environmental risk factors and common clinical electrophysiology.

    Science.gov (United States)

    Port, Russell G; Gandal, Michael J; Roberts, Timothy P L; Siegel, Steven J; Carlson, Gregory C

    2014-01-01

    Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD). Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents). Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in vivo and ex vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD.

  7. Convergence of Circuit Dysfunction in ASD: A common bridge between diverse genetic and environmental risk factors and common clinical neurophysiology.

    Directory of Open Access Journals (Sweden)

    Russell G Port

    2014-12-01

    Full Text Available Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD. Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents. Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in-vivo and ex-vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD.

  8. Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival

    Directory of Open Access Journals (Sweden)

    Sung Hyuna

    2012-05-01

    Full Text Available Abstract Background Although the role of microRNA’s (miRNA’s biogenesis pathway genes in cancer development and progression has been well established, the association between genetic variants of this pathway genes and breast cancer survival is still unknown. Methods We used genotype data available from a previously conducted case–control study to investigate association between common genetic variations in miRNA biogenesis pathway genes and breast cancer survival. We investigated the possible associations between 41 germ-line single-nucleotide polymorphisms (SNPs and both disease free survival (DFS and overall survival (OS among 488 breast cancer patients. During the median follow-up of 6.24 years, 90 cases developed disease progression and 48 cases died. Results Seven SNPs were significantly associated with breast cancer survival. Two SNPs in AGO2 (rs11786030 and rs2292779 and DICER1 rs1057035 were associated with both DFS and OS. Two SNPs in HIWI (rs4759659 and rs11060845 and DGCR8 rs9606250 were associated with DFS, while DROSHA rs874332 and GEMIN4 rs4968104 were associated with only OS. The most significant association was observed in variant allele of AGO2 rs11786030 with 2.62-fold increased risk of disease progression (95% confidence interval (CI, 1.41-4.88 and in minor allele homozygote of AGO2 rs2292779 with 2.94-fold increased risk of death (95% CI, 1.52-5.69. We also found cumulative effects of SNPs on DFS and OS. Compared to the subjects carrying 0 to 2 high-risk genotypes, those carrying 3 or 4–6 high-risk genotypes had an increased risk of disease progression with a hazard ratio of 2.16 (95% CI, 1.18- 3.93 and 4.47 (95% CI, 2.45- 8.14, respectively (P for trend, 6.11E-07. Conclusions Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer survival. Further studies in larger sample size and functional characterizations are warranted to validate these results.

  9. Genetic structure of the Common Eider in the western Aleutian Islands prior to fox eradication

    Science.gov (United States)

    Sonsthagen, Sarah A.; Talbot, Sandra L.; Wilson, Robert E.; Petersen, Margaret R.; Williams, Jeffrey C.; Byrd, G. Vernon; McCracken, Kevin G.

    2013-01-01

    Since the late 18th century bird populations residing in the Aleutian Archipelago have been greatly reduced by introduced arctic foxes (Alopex lagopus). We analyzed data from microsatellite, nuclear intron, and mitochondrial (mtDNA) loci to examine the spatial genetic structure, demography, and gene flow among four Aleutian Island populations of the Common Eider (Somateria mollissima) much reduced by introduced foxes. In mtDNA, we found high levels of genetic structure within and between island groups (ΦST = 0.643), but we found no population subdivision in microsatellites or nuclear introns. Differences in genetic structure between the mitochondrial and nuclear genomes are consistent with the Common Eider's breeding and winter biology, as females are highly philopatric and males disperse. Nevertheless, significant differences between islands in the mtDNA of males and marginal significance (P =0.07) in the Z-linked locus Smo 1 suggest that males may also have some level of fidelity to island groups. Severe reduction of populations by the fox, coupled with females' high philopatry, may have left the genetic signature of a bottleneck effect, resulting in the high levels of genetic differentiation observed in mtDNA (ΦST = 0.460–0.807) between islands only 440 km apart. Reestablishment of the Common Eider following the fox's eradication was likely through recruitment from within the islands and bolstered by dispersal from neighboring islands, as suggested by the lack of genetic structure and asymmetry in gene flow between Attu and the other Near Islands.

  10. ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties.

    Science.gov (United States)

    St Pourcain, B; Robinson, E B; Anttila, V; Sullivan, B B; Maller, J; Golding, J; Skuse, D; Ring, S; Evans, D M; Zammit, S; Fisher, S E; Neale, B M; Anney, R J L; Ripke, S; Hollegaard, M V; Werge, T; Ronald, A; Grove, J; Hougaard, D M; Børglum, A D; Mortensen, P B; Daly, M J; Davey Smith, G

    2017-01-03

    Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, N⩽5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.Molecular Psychiatry advance online

  11. RF kicker cavity to increase control in common transport lines

    Science.gov (United States)

    Douglas, David R.; Ament, Lucas J. P.

    2017-04-18

    A method of controlling e-beam transport where electron bunches with different characteristics travel through the same beam pipe. An RF kicker cavity is added at the beginning of the common transport pipe or at various locations along the common transport path to achieve independent control of different bunch types. RF energy is applied by the kicker cavity kicks some portion of the electron bunches, separating the bunches in phase space to allow independent control via optics, or separating bunches into different beam pipes. The RF kicker cavity is operated at a specific frequency to enable kicking of different types of bunches in different directions. The phase of the cavity is set such that the selected type of bunch passes through the cavity when the RF field is at a node, leaving that type of bunch unaffected. Beam optics may be added downstream of the kicker cavity to cause a further separation in phase space.

  12. Genetic Algorithm based Decentralized PI Type Controller: Load Frequency Control

    Science.gov (United States)

    Dwivedi, Atul; Ray, Goshaidas; Sharma, Arun Kumar

    2016-12-01

    This work presents a design of decentralized PI type Linear Quadratic (LQ) controller based on genetic algorithm (GA). The proposed design technique allows considerable flexibility in defining the control objectives and it does not consider any knowledge of the system matrices and moreover it avoids the solution of algebraic Riccati equation. To illustrate the results of this work, a load-frequency control problem is considered. Simulation results reveal that the proposed scheme based on GA is an alternative and attractive approach to solve load-frequency control problem from both performance and design point of views.

  13. Populus trichocarpa cell wall chemistry and ultrastructure trait variation, genetic control and genetic correlations.

    Science.gov (United States)

    Porth, Ilga; Klápště, Jaroslav; Skyba, Oleksandr; Lai, Ben S K; Geraldes, Armando; Muchero, Wellington; Tuskan, Gerald A; Douglas, Carl J; El-Kassaby, Yousry A; Mansfield, Shawn D

    2013-02-01

    The increasing ecological and economical importance of Populus species and hybrids has stimulated research into the investigation of the natural variation of the species and the estimation of the extent of genetic control over its wood quality traits for traditional forestry activities as well as the emerging bioenergy sector. A realized kinship matrix based on informative, high-density, biallelic single nucleotide polymorphism (SNP) genetic markers was constructed to estimate trait variance components, heritabilities, and genetic and phenotypic correlations. Seventeen traits related to wood chemistry and ultrastructure were examined in 334 9-yr-old Populus trichocarpa grown in a common-garden plot representing populations spanning the latitudinal range 44° to 58.6°. In these individuals, 9342 SNPs that conformed to Hardy-Weinberg expectations were employed to assess the genomic pair-wise kinship to estimate narrow-sense heritabilities and genetic correlations among traits. The range-wide phenotypic variation in all traits was substantial and several trait heritabilities were > 0.6. In total, 61 significant genetic and phenotypic correlations and a network of highly interrelated traits were identified. The high trait variation, the evidence for moderate to high heritabilities and the identification of advantageous trait combinations of industrially important characteristics should aid in providing the foundation for the enhancement of poplar tree breeding strategies for modern industrial use.

  14. 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...

  15. Genetic mechanisms and age-related macular degeneration: common variants, rare variants, copy number variations, epigenetics, and mitochondrial genetics

    Directory of Open Access Journals (Sweden)

    Liu Melissa M

    2012-08-01

    Full Text Available Abstract Age-related macular degeneration (AMD is a complex and multifaceted disease involving contributions from both genetic and environmental influences. Previous work exploring the genetic contributions of AMD has implicated numerous genomic regions and a variety of candidate genes as modulators of AMD susceptibility. Nevertheless, much of this work has revolved around single-nucleotide polymorphisms (SNPs, and it is apparent that a significant portion of the heritability of AMD cannot be explained through these mechanisms. In this review, we consider the role of common variants, rare variants, copy number variations, epigenetics, microRNAs, and mitochondrial genetics in AMD. Copy number variations in regulators of complement activation genes (CFHR1 and CFHR3 and glutathione S transferase genes (GSTM1 and GSTT1 have been associated with AMD, and several additional loci have been identified as regions of potential interest but require further evaluation. MicroRNA dysregulation has been linked to the retinal pigment epithelium degeneration in geographic atrophy, ocular neovascularization, and oxidative stress, all of which are hallmarks in the pathogenesis of AMD. Certain mitochondrial DNA haplogroups and SNPs in mitochondrially encoded NADH dehydrogenase genes have also been associated with AMD. The role of these additional mechanisms remains only partly understood, but the importance of their further investigation is clear to elucidate more completely the genetic basis of AMD.

  16. Genetic and environmental control of salmonella invasion.

    Science.gov (United States)

    Altier, Craig

    2005-02-01

    An early step in the pathogenesis of non-typhoidal Salmonella species is the ability to penetrate the intestinal epithelial monolayer. This process of cell invasion requires the production and transport of secreted effector proteins by a type III secretion apparatus encoded in Salmonella pathogenicity island I (SPI-1). The control of invasion involves a number of genetic regulators and environmental stimuli in complex relationships. SPI-1 itself encodes several transcriptional regulators (HilA, HilD, HilC, and InvF) with overlapping sets of target genes. These regulators are, in turn, controlled by both positive and regulators outside SPI-1, including the two-component regulators BarA/SirA and PhoP/Q, and the csr post-transcriptional control system. Additionally, several environmental conditions are known to regulate invasion, including pH, osmolarity, oxygen tension, bile, Mg2+ concentration, and short chain fatty acids. This review will discuss the current understanding of invasion control, with emphasis on the interaction of environmental factors with genetic regulators that leads to productive infection.

  17. Citizens in the commons: blood and genetics in the making of the civic.

    Science.gov (United States)

    Reddy, Deepa S

    2013-01-01

    This essay is based on ethnographic fieldwork conducted with the Indian community in Houston, as part of a NIH/NHGRI-sponsored ethics study and sample collection initiative entitled 'Indian and Hindu Perspectives on Genetic Variation Research.' Taking a cue from my Indian interlocutors who largely support and readily respond to such initiatives on the grounds that they will undoubtedly serve 'humanity' and the common good, I explore notions of the commons that are created in the process of soliciting blood for genetic research. How does blood become the stuff of which a civic discourse is made? How do idealistic individual appeals to donate blood, ethics research protocols, open-source databases, debates on approaches to genetic research, patents and Intellectual Property regulations, markets and the nation-state itself variously engage, limit or further ideas of the common good? Moving much as my interlocutors do, between India and the United States, I explore the nature of the commons that is both imagined and pragmatically reckoned in both local and global diasporic contexts.

  18. An Optimization System with Parallel Processing for Reducing Common-Mode Current on Electronic Control Unit

    Science.gov (United States)

    Okazaki, Yuji; Uno, Takanori; Asai, Hideki

    In this paper, we propose an optimization system with parallel processing for reducing electromagnetic interference (EMI) on electronic control unit (ECU). We adopt simulated annealing (SA), genetic algorithm (GA) and taboo search (TS) to seek optimal solutions, and a Spice-like circuit simulator to analyze common-mode current. Therefore, the proposed system can determine the adequate combinations of the parasitic inductance and capacitance values on printed circuit board (PCB) efficiently and practically, to reduce EMI caused by the common-mode current. Finally, we apply the proposed system to an example circuit to verify the validity and efficiency of the system.

  19. Common Rail System for GDI Engines Modelling, Identification, and Control

    CERN Document Server

    Fiengo, Giovanni; Palladino, Angelo; Giglio, Veniero

    2013-01-01

    Progressive reductions in vehicle emission requirements have forced the automotive industry to invest in research and development of alternative control strategies. Continual control action exerted by a dedicated electronic control unit ensures that best performance in terms of pollutant emissions and power density is married with driveability and diagnostics. Gasoline direct injection (GDI) engine technology is a way to attain these goals. This brief describes the functioning of a GDI engine equipped with a common rail (CR) system, and the devices necessary to run test-bench experiments in detail. The text should prove instructive to researchers in engine control and students are recommended to this brief as their first approach to this technology. Later chapters of the brief relate an innovative strategy designed to assist with the engine management system; injection pressure regulation for fuel pressure stabilization in the CR fuel line is proposed and validated by experiment. The resulting control scheme ...

  20. Role of common sarcomeric gene polymorphisms in genetic susceptibility to left ventricular dysfunction

    Indian Academy of Sciences (India)

    SURENDRA KUMAR; AVSHESH MISHRA; ANSHIKA SRIVASTAVA; MANSI BHATT; N. GARG; S. K. AGARWAL; SHANTANU PANDE; BALRAJ MITTAL

    2016-06-01

    Mutations in sarcomeric genes are common genetic cause of cardiomyopathies. An intronic 25-bp deletion in cardiac myosin binding protein C (MYBPC3) at 3' region is associated with dilated and hypertrophic cardiomyopathies in Southeast Asia. However, the frequency of sarcomeric gene polymorphisms and associated clinical presentation have not been established with left ventricular dysfunction (LVD). Therefore, the aim of the present study was to explore the association of MYBPC3 25-bp deletion, titin (TTN) 18 bp I/D, troponin T type 2 (TNNT2) 5 bp I/D and myospryn K2906N polymorphisms with LVD. This study includes 988 consecutive patients with angiographically confirmed coronary artery disease (CAD) and 300 healthy controls. Among the 988 CAD patients, 253 with reduced left ventricle ejection fraction (LVEF≤45%) were categorized as LVD. MYBPC3 25-bp deletion,TTN 18 bp I/D and TNNT25 bp I/D polymorphisms were determined by direct polymerase chain reaction method, while myospryn K2906N polymorphism by TaqMan assay. Our results showed that MYBPC3 25-bpdeletion polymorphism was significantly associated with elevated risk of LVD (LVEF <45) (healthy controls versus LVD: OR= 3.85,P<0.001; and nonLVD versus LVD: OR=1.65,P=0.035), while TTN 18 bp I/D, TNNT25bpI/Dand myospryn K2906N polymorphisms did not show any significant association with LVD. The results also showed that MYBPC3 25-bp deletion polymorphism was significantly associated with other parameters of LV remodelling, i.e. LV dimensions (LV end diastole dimension, LVEDD: P= 0.037 and LV end systolic dimension, LVESD: P= 0.032).Our data suggests that MYBPC3 25-bp deletion may play significant role in conferring LVD as well as CAD risk in north Indian population

  1. Common genetic variants in NEFL influence gene expression and neuroblastoma risk.

    Science.gov (United States)

    Capasso, Mario; Diskin, Sharon; Cimmino, Flora; Acierno, Giovanni; Totaro, Francesca; Petrosino, Giuseppe; Pezone, Lucia; Diamond, Maura; McDaniel, Lee; Hakonarson, Hakon; Iolascon, Achille; Devoto, Marcella; Maris, John M

    2014-12-01

    The genetic etiology of sporadic neuroblastoma is still largely obscure. In a genome-wide association study, we identified single-nucleotide polymorphisms (SNP) associated with neuroblastoma at the CASC15, BARD1, LMO1, DUSP12, HSD17B12, HACE1, and LIN28B gene loci, but these explain only a small fraction of neuroblastoma heritability. Other neuroblastoma susceptibility genes are likely hidden among signals discarded by the multiple testing corrections. In this study, we evaluated eight additional genes selected as candidates for further study based on proven involvement in neuroblastoma differentiation. SNPs at these candidate genes were tested for association with disease susceptibility in 2,101 cases and 4,202 controls, with the associations found replicated in an independent cohort of 459 cases and 809 controls. Replicated associations were further studied for cis-effect using gene expression, transient overexpression, silencing, and cellular differentiation assays. The neurofilament gene NEFL harbored three SNPs associated with neuroblastoma (rs11994014: Pcombined = 0.0050; OR, 0.88; rs2979704: Pcombined = 0.0072; OR, 0.87; rs1059111: Pcombined = 0.0049; OR, 0.86). The protective allele of rs1059111 correlated with increased NEFL expression. Biologic investigations showed that ectopic overexpression of NEFL inhibited cell growth specifically in neuroblastoma cells carrying the protective allele. NEFL overexpression also enhanced differentiation and impaired the proliferation and anchorage-independent growth of cells with protective allele and basal NEFL expression, while impairing invasiveness and proliferation of cells homozygous for the risk genotype. Clinically, high levels of NEFL expression in primary neuroblastoma specimens were associated with better overall survival (P = 0.03; HR, 0.68). Our results show that common variants of NEFL influence neuroblastoma susceptibility and they establish that NEFL expression influences disease initiation and

  2. Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses.

    Science.gov (United States)

    Visscher, P M; Goddard, M E; Derks, E M; Wray, N R

    2012-05-01

    In this article, we review some of the data that contribute to our understanding of the genetic architecture of psychiatric disorders. These include results from evolutionary modelling (hence no data), the observed recurrence risk to relatives and data from molecular markers. We briefly discuss the common-disease common-variant hypothesis, the success (or otherwise) of genome-wide association studies, the evidence for polygenic variance and the likely success of exome and whole-genome sequencing studies. We conclude that the perceived dichotomy between 'common' and 'rare' variants is not only false, but unhelpful in making progress towards increasing our understanding of the genetic basis of psychiatric disorders. Strong evidence has been accumulated that is consistent with the contribution of many genes to risk of disease, across a wide range of allele frequencies and with a substantial proportion of genetic variation in the population in linkage disequilibrium with single-nucleotide polymorphisms (SNPs) on commercial genotyping arrays. At the same time, most causal variants that segregate in the population are likely to be rare and in total these variants also explain a significant proportion of genetic variation. It is the combination of allele frequency, effect size and functional characteristics that will determine the success of new experimental paradigms such as whole exome/genome sequencing to detect such loci. Empirical results suggest that roughly half the genetic variance is tagged by SNPs on commercial genome-wide chips, but that individual causal variants have a small effect size, on average. We conclude that larger experimental sample sizes are essential to further our understanding of the biology underlying psychiatric disorders.

  3. Neuroinformatic Analyses of Common and Distinct Genetic Components Associated with Major Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Amit eLotan

    2014-11-01

    Full Text Available Major neuropsychiatric disorders are highly heritable, with mounting evidence suggesting that these disorders share overlapping sets of molecular and cellular underpinnings. In the current article we systematically test the degree of genetic commonality across six major neuropsychiatric disorders—attention deficit hyperactivity disorder, anxiety disorders, autistic spectrum disorders, bipolar disorder, major depressive disorder and schizophrenia. We curated a well-vetted list of genes based on large-scale human genetic studies and verified their appearance on the NHGRI catalog of published genome-wide association studies. A total of 180 genes were accepted into the analysis on the basis of low but liberal GWAS p-values (<10-5. 22% of genes overlapped two or more disorders. The most widely shared subset of genes—common to five of six disorders–included ANK3, AS3MT, CACNA1C, CACNB2, CNNM2, CSMD1, DPCR1, ITIH3, NT5C2, PPP1R11, SYNE1, TCF4, TENM4, TRIM26, and ZNRD1. Using a suite of neuroinformatic resources, we showed that many of the shared genes are implicated in the postsynaptic density, expressed in immune tissues and co-expressed in developing human brain.. Using a translational cross-species approach, we detected two distinct genetic components that were both shared by each of the six disorders; the 1st component is involved in CNS development, neural projections and synaptic transmission, while the 2nd is implicated in various cytoplasmic organelles and cellular processes. Combined, these genetic components account for 20–30% of the genetic load. The remaining risk is conferred by distinct, disorder-specific variants. Nevertheless, the convergence of different analytical approaches on similar targets may bear important implications. Thus, although adding mostly confirmatory findings, higher resolution of shared and unique genetic factors provided in this manuscript could ultimately translate into improved diagnosis and treatment of

  4. Genetic variation of common walnut (Juglans regia in Piedmont, Northwestern Italy

    Directory of Open Access Journals (Sweden)

    Ferrazzini D

    2007-12-01

    Full Text Available The European or common walnut is a large tree prized as a multipurpose species: it provides valuable timber and produces a high-quality edible nut. The diffusion of the species in Italy has been largely influenced by the human activity, mainly through germplasm movement, selection of genotypes most suited for wood or fruit production and adaptation induced on fruit crop reproductive materials. As a consequence, genetic variability has been reduced, so that programs aimed at its preservation appear of the utmost importance. 104 walnut plants growing in Piedmont, northwestern Italy, were investigated through genetic variation scored at RAPD loci, yielded by PCR amplification of 10 decamer primers. Among the 101 studied loci, only 53 were polymorphic, showing a low level of genetic variation within the studied material. Genetic differentiation was estimated both at individual and geographical area level. Only in few cases trees growing in the same area showed to be genetically similar, while the differentiation between areas accounted for about 10% of the total variation, according to AMOVA. No significant correlation was found between genetic and geographic distances. The results of the study showed that also in Piedmont (such as it was already demonstrated in other parts of Italy the distribution of common walnut is a direct consequence of the human activity. The selection of individual trees, to be used as basic materials for seed supply, should therefore be based mainly on phenotypic traits, rather than ecological features of the location: in species characterized by artificial diffusion, the adoption of Region of Provenance has a scarce significance and prominence should be given to the phenotype selection.

  5. Shared genetic variants suggest common pathways in allergy and autoimmune diseases

    DEFF Research Database (Denmark)

    Kreiner-Møller, Eskil; Waage, Johannes; Standl, Marie

    2016-01-01

    Background: The relationship between allergy and autoimmune disorders is complex and poorly understood. Objective: To investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. Methods: We meta-analyzed two GWAS on self......-reported allergy and sensitization comprising a total of 62,330 individuals. These results were used to calculate enrichment for SNPs previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites, and characterized...... commonalities in the variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DHS data, and compared the allergy data with all known diseases. Conclusion: Among 290 loci previously associated with 16...

  6. Genetics of diabetic nephropathy: are there clues to the understanding of common kidney diseases?

    Science.gov (United States)

    Conway, B R; Maxwell, A P

    2009-01-01

    Diabetic nephropathy is the most common cause of end-stage renal disease in the Western world. There is evidence for a genetic susceptibility to diabetic kidney disease, but despite intensive research efforts it has proved difficult to identify the causative genes. Improvements in genotyping technologies have made genome-wide association studies (GWAS), employing hundreds of thousands of single nucleotide polymorphisms, affordable. Recently, such scans have advanced understanding of the genetics of common complex diseases, finding more than 100 novel susceptibility variants for diverse disorders including type 1 and 2 diabetes, coronary heart disease, Crohn's disease and rheumatoid arthritis. In this review, type 2 diabetes is highlighted to illustrate how genome-wide association studies have been used to study the genetics of complex multifactorial conditions; in addition, diabetic nephropathy will be used to demonstrate how similar scans could be employed to detect genetic factors predisposing to kidney disease. The identification of such variants would permit early identification of atrisk patients, enabling targeting of therapy and a move towards primary prevention. In addition, these powerful research methodologies may identify genes that were not previously known to predispose to nephropathy, thereby enhancing our understanding of the pathophysiology of renal disorders and potentially leading to novel therapeutic approaches.

  7. Geochemical, Genetic, and Community Controls on Mercury

    Energy Technology Data Exchange (ETDEWEB)

    Wall, Judy D.

    2014-11-10

    The sulfate-reducing bacteria (SRB) are soil bacteria that share two common characteristics, strict anaerobiosis and the ability to respire sulfate. The metabolic activities of these bacteria play significant roles in the global sulfur cycle, anaerobic degradation of biomass, biological metal corrosion in the environment and, recently, degradation of toxic compounds. The accumulation of evidence suggests these bacteria are also key to the production of the neurotoxin methylmercury in environmental settings. We propose to use our experience with the development of genetics in sulfate-reducing bacteria of the genus Desulfovibrio to create mutations that will eliminate the methylation of mercury, thereby identifying the genes essential for this process. This information may allow the environmental monitoring of the mercury methylation potential to learn the location and quantity of the production this toxin. From these data, more accurate predictive models of mercury cycling can be generated.

  8. Neuroinformatic Analyses of Common and Distinct Genetic Components Associated with Major Neuropsychiatric Disorders

    OpenAIRE

    Amit eLotan; Michaela eFenckova; Janita eBralten; Aet eAlttoa; Luanna eDixson; Williams, Robert W.; Monique evan der Voet

    2014-01-01

    Major neuropsychiatric disorders are highly heritable, with mounting evidence suggesting that these disorders share overlapping sets of molecular and cellular underpinnings. In the current article we systematically test the degree of genetic commonality across six major neuropsychiatric disorders—attention deficit hyperactivity disorder, anxiety disorders, autistic spectrum disorders, bipolar disorder, major depressive disorder and schizophrenia. We curated a well-vetted list of genes based o...

  9. Disentangling genetic vs. environmental causes of sex determination in the common frog, Rana temporaria

    OpenAIRE

    Merilä Juha; Miura Ikuo; Matsuba Chikako

    2008-01-01

    Abstract Background Understanding of sex ratio dynamics in a given species requires understanding its sex determination system, as well as access for reliable tools for sex identification at different life stages. As in the case of many other amphibians, the common frogs (Rana temporaria) do not have well differentiated sex chromosomes, and an identification of individuals' genetic sex may be complicated by sex reversals. Here, we report results of studies shedding light on the sex determinat...

  10. Web-based, participant-driven studies yield novel genetic associations for common traits.

    OpenAIRE

    Nicholas Eriksson; J Michael Macpherson; Joyce Y Tung; Hon, Lawrence S.; Brian Naughton; Serge Saxonov; Linda Avey; Anne Wojcicki; Itsik Pe'er; Joanna Mountain

    2010-01-01

    Despite the recent rapid growth in genome-wide data, much of human variation remains entirely unexplained. A significant challenge in the pursuit of the genetic basis for variation in common human traits is the efficient, coordinated collection of genotype and phenotype data. We have developed a novel research framework that facilitates the parallel study of a wide assortment of traits within a single cohort. The approach takes advantage of the interactivity of the Web both to gather data and...

  11. A HapMap harvest of insights into the genetics of common disease.

    Science.gov (United States)

    Manolio, Teri A; Brooks, Lisa D; Collins, Francis S

    2008-05-01

    The International HapMap Project was designed to create a genome-wide database of patterns of human genetic variation, with the expectation that these patterns would be useful for genetic association studies of common diseases. This expectation has been amply fulfilled with just the initial output of genome-wide association studies, identifying nearly 100 loci for nearly 40 common diseases and traits. These associations provided new insights into pathophysiology, suggesting previously unsuspected etiologic pathways for common diseases that will be of use in identifying new therapeutic targets and developing targeted interventions based on genetically defined risk. In addition, HapMap-based discoveries have shed new light on the impact of evolutionary pressures on the human genome, suggesting multiple loci important for adapting to disease-causing pathogens and new environments. In this review we examine the origin, development, and current status of the HapMap; its prospects for continued evolution; and its current and potential future impact on biomedical science.

  12. Multicollinearity in spatial genetics: separating the wheat from the chaff using commonality analyses.

    Science.gov (United States)

    Prunier, J G; Colyn, M; Legendre, X; Nimon, K F; Flamand, M C

    2015-01-01

    Direct gradient analyses in spatial genetics provide unique opportunities to describe the inherent complexity of genetic variation in wildlife species and are the object of many methodological developments. However, multicollinearity among explanatory variables is a systemic issue in multivariate regression analyses and is likely to cause serious difficulties in properly interpreting results of direct gradient analyses, with the risk of erroneous conclusions, misdirected research and inefficient or counterproductive conservation measures. Using simulated data sets along with linear and logistic regressions on distance matrices, we illustrate how commonality analysis (CA), a detailed variance-partitioning procedure that was recently introduced in the field of ecology, can be used to deal with nonindependence among spatial predictors. By decomposing model fit indices into unique and common (or shared) variance components, CA allows identifying the location and magnitude of multicollinearity, revealing spurious correlations and thus thoroughly improving the interpretation of multivariate regressions. Despite a few inherent limitations, especially in the case of resistance model optimization, this review highlights the great potential of CA to account for complex multicollinearity patterns in spatial genetics and identifies future applications and lines of research. We strongly urge spatial geneticists to systematically investigate commonalities when performing direct gradient analyses.

  13. Evaluation of Genetic Diversity of Sichuan Common Wheat Landraces in China by SSR Markers

    Institute of Scientific and Technical Information of China (English)

    LI Wei; BIAN Chun-mei; WEI Yu-ming; LIU An-jun; CHEN Guo-yue; PU Zhi-en; LIU Ya-xi; ZHENG You-liang

    2013-01-01

    Genetic diversity of 62 Sichuan wheat landraces accessions of China was investigated by agronomic traits and SSR markers. The landrace population showed the characters of higher tiller capability and more kernels/spike, especially tiller no./plant of six accessions was over 40 and kernels/spike of three accessions was more than 70. A total of 547 alleles in 124 polymorphic loci were detected with an average of 4.76 alleles per locus by 114 SSR markers. Parameters analysis indicated that the genetic diversity ranked as genome A>genome B>genome D, and the homoeologous groups ranked as 5>4>3>1>2>7>6 based on genetic richness (Ri). Furthermore, chromosomes 2A, 1B and 3D had more diversity than that of chromosomes 4A, 7A and 6B. The variation of SSR loci on chromosomes 1B, 2A, 2D, 3B, and 4B implied that, in the past, different selective pressures might have acted on different chromosome regions of these landraces. Our results suggested that Sichuan common wheat landraces is a useful genetic resource for genetic research and wheat improvement.

  14. Genetic variability of the common Snook Centropomus undecimalis (Perciformes: Centropomidae) in connected marine and riverine environments.

    Science.gov (United States)

    Hernández-Vidal, Ulises; Lesher-Gordillo, Julia; Contreras-Sánchez, Wilfrido M; Chiappa-Carrara, Xavier

    2014-06-01

    The Common Snook, Centropomus undecimalis, inhabits riverine and marine areas of Southern Gulf of Mexico, where it is subject to intense use and exploitation. It has been reported that the genetic identification of fish stocks constitutes a valuable tool for wild population management; nevertheless, there is no available information on the genetic identification on fish stocks of this species in the region. The aim of this study was to determine the genetic relationship between C. undecimalis captured in marine and freshwater environments of the Gulf of Mexico and the San Pedro River. For this, muscle tissue samples of 79 specimens were obtained from areas located more than 300km apart. The genotype of each individual was determined using seven microsatellite primer pairs. Five primers amplified efficiently presenting between six and 28 alleles per locus. High levels of heterozygosis were observed in samples from both environments. Deviation from HWE due to an excess of heterozygotes was observed. The values of genetic difference indicate an absence of population structure (F(ST) = 0.0075 and R(ST) = (0.016, p = 0.051) and similarity in the allele frequencies, defined by Nei's index (0.805). Data showed the existence of a high gene flow due to the number of migrants (Nm = 18.7). Our results suggest that individuals living in these environments belong to the same genetic population. We suggest the development of management and protection plans for this fish species population in the wild.

  15. A dense genetic linkage map for common carp and its integration with a BAC-based physical map.

    Directory of Open Access Journals (Sweden)

    Lan Zhao

    Full Text Available BACKGROUND: Common carp (Cyprinus carpio is one of the most important aquaculture species with an annual global production of 3.4 million metric tons. It is also an important ornamental species as well as an important model species for aquaculture research. To improve the economically important traits of this fish, a number of genomic resources and genetic tools have been developed, including several genetic maps and a bacterial artificial chromosome (BAC-based physical map. However, integrated genetic and physical maps are not available to study quantitative trait loci (QTL and assist with fine mapping, positional cloning and whole genome sequencing and assembly. The objective of this study was to integrate the currently available BAC-based physical and genetic maps. RESULTS: The genetic map was updated with 592 novel markers, including 312 BAC-anchored microsatellites and 130 SNP markers, and contained 1,209 genetic markers on 50 linkage groups, spanning 3,565.9 cM in the common carp genome. An integrated genetic and physical map of the common carp genome was then constructed, which was composed of 463 physical map contigs and 88 single BACs. Combined lengths of the contigs and single BACs covered a physical length of 498.75 Mb, or around 30% of the common carp genome. Comparative analysis between common carp and zebrafish genomes was performed based on the integrated map, providing more insights into the common carp specific whole genome duplication and segmental rearrangements in the genome. CONCLUSION: We integrated a BAC-based physical map to a genetic linkage map of common carp by anchoring BAC-associated genetic markers. The density of the genetic linkage map was significantly increased. The integrated map provides a tool for both genetic and genomic studies of common carp, which will help us to understand the genomic architecture of common carp and facilitate fine mapping and positional cloning of economically important traits for

  16. Genetic and physiological controls of growth under water deficit.

    Science.gov (United States)

    Tardieu, François; Parent, Boris; Caldeira, Cecilio F; Welcker, Claude

    2014-04-01

    The sensitivity of expansive growth to water deficit has a large genetic variability, which is higher than that of photosynthesis. It is observed in several species, with some genotypes stopping growth in a relatively wet soil, whereas others continue growing until the lower limit of soil-available water. The responses of growth to soil water deficit and evaporative demand share an appreciable part of their genetic control through the colocation of quantitative trait loci as do the responses of the growth of different organs to water deficit. This result may be caused by common mechanisms of action discussed in this paper (particularly, plant hydraulic properties). We propose that expansive growth, putatively linked to hydraulic processes, determines the sink strength under water deficit, whereas photosynthesis determines source strength. These findings have large consequences for plant modeling under water deficit and for the design of breeding programs.

  17. Designing a common real-time controller for VLT applications

    Science.gov (United States)

    Bauvir, Bertrand; Wallander, Anders; Duhoux, Philippe; Huxley, Alexis; Karban, Robert

    2004-09-01

    The increasing number of digital control applications in the context of the VLT, and particularly the VLT Interferometer, brought the need to find a common solution to address the problems of performance and maintainability. Tools for Advanced Control (TAC) aims at helping both control and software engineers in the design and prototyping of real-time control applications by providing them with a set of standard functions and an easy way to combine them to create complex control algorithms. In this paper we describe the software architecture and design of TAC, the VLT standard for digital control applications. Algorithms are described at schematic level and take the form of a set of interconnected function blocks. Periodical execution of the algorithm as well as features like runtime modification of parameters and probing of internal data are also managed by TAC, allowing the application designers to avoid spending time writing low value software code and therefore focus on application-specific concerns. We also summarize the results achieved on the first actual applications using TAC, to manage real-time control or digital signal processing algorithms, currently deployed and being commissioned at Paranal Observatory.

  18. The role of genetics in fisheries management under the E.U. common fisheries policy.

    Science.gov (United States)

    Casey, J; Jardim, E; Martinsohn, J Th

    2016-12-01

    Exploitation of fish and shellfish stocks by the European Union fishing fleet is managed under the Common Fisheries Policy (CFP), which aims to ensure that fishing and aquaculture are environmentally, economically and socially sustainable and that they provide a source of healthy food for E.U. citizens. A notable feature of the CFP is its legally enshrined requirement for sound scientific advice to underpin its objectives. The CFP was first conceived in 1970 when it formed part of the Common Agricultural Policy. Its formal inception as a stand-alone regulation occurred in 1983 and since that time, the CFP has undergone reforms in 1992, 2002 and 2013, each time bringing additional challenges to the scientific advisory process as the scope of the advice increased in response to changing objectives arising from E.U. regulations and commitments to international agreements. This paper reviews the influence that genetics has had on fish stock assessments and the provision of management advice for European fisheries under successive reforms of the CFP. The developments in genetics since the inception of the CFP have given rise to a diverse and versatile set of genetic techniques that have the potential to provide significant added value to fisheries assessments and the scientific advisory process. While in some cases, notably Pacific salmon Oncorhynchus spp., genetics appear to be very well integrated into existing management schemes, it seems that for marine fishes, discussions on the use of genetics and genomics for fisheries management are often driven by the remarkable technological progress in this field, rather than imminent needs emerging from policy frameworks. An example is the recent suggestion to use environmental (e)DNA for monitoring purposes. While there is no denying that state-of-the-art genetic and genomic approaches can and will be of value to address a number of issues relevant for the management and conservation of marine renewable natural resources, a

  19. Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42 103 individuals

    NARCIS (Netherlands)

    Dunlop, Malcolm G.; Tenesa, Albert; Farrington, Susan M.; Ballereau, Stephane; Brewster, David H.; Koessler, Thibaud; Pharoah, Paul; Schafmayer, Clemens; Hampe, Jochen; Voelzke, Henry; Chang-Claude, Jenny; Hoffmeister, Michael; Brenner, Hermann; von Holst, Susanna; Picelli, Simone; Lindblom, Annika; Jenkins, Mark A.; Hopper, John L.; Casey, Graham; Duggan, David; Newcomb, Polly A.; Abuli, Anna; Bessa, Xavier; Ruiz-Ponte, Clara; Castellvi-Bel, Sergi; Niittymaeki, Iina; Tuupanen, Sari; Karhu, Auli; Aaltonen, Lauri; Zanke, Brent; Hudson, Tom; Gallinger, Steven; Barclay, Ella; Martin, Lynn; Gorman, Maggie; Carvajal-Carmona, Luis; Walther, Axel; Kerr, David; Lubbe, Steven; Broderick, Peter; Chandler, Ian; Pittman, Alan; Penegar, Steven; Campbell, Harry; Tomlinson, Ian; Houlston, Richard S.

    2013-01-01

    Objective Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other r

  20. Phenotype-Based Genetic Association Studies (PGAS—Towards Understanding the Contribution of Common Genetic Variants to Schizophrenia Subphenotypes

    Directory of Open Access Journals (Sweden)

    Hannelore Ehrenreich

    2014-02-01

    Full Text Available Neuropsychiatric diseases ranging from schizophrenia to affective disorders and autism are heritable, highly complex and heterogeneous conditions, diagnosed purely clinically, with no supporting biomarkers or neuroimaging criteria. Relying on these “umbrella diagnoses”, genetic analyses, including genome-wide association studies (GWAS, were undertaken but failed to provide insight into the biological basis of these disorders. “Risk genotypes” of unknown significance with low odds ratios of mostly <1.2 were extracted and confirmed by including ever increasing numbers of individuals in large multicenter efforts. Facing these results, we have to hypothesize that thousands of genetic constellations in highly variable combinations with environmental co-factors can cause the individual disorder in the sense of a final common pathway. This would explain why the prevalence of mental diseases is so high and why mutations, including copy number variations, with a higher effect size than SNPs, constitute only a small part of variance. Elucidating the contribution of normal genetic variation to (disease phenotypes, and so re-defining disease entities, will be extremely labor-intense but crucial. We have termed this approach PGAS (“phenotype-based genetic association studies”. Ultimate goal is the definition of biological subgroups of mental diseases. For that purpose, the GRAS (Göttingen Research Association for Schizophrenia data collection was initiated in 2005. With >3000 phenotypical data points per patient, it comprises the world-wide largest currently available schizophrenia database (N > 1200, combining genome-wide SNP coverage and deep phenotyping under highly standardized conditions. First PGAS results on normal genetic variants, relevant for e.g., cognition or catatonia, demonstrated proof-of-concept. Presently, an autistic subphenotype of schizophrenia is being defined where an unfortunate accumulation of normal genotypes, so

  1. Common biological networks underlie genetic risk for alcoholism in African- and European-American populations.

    Science.gov (United States)

    Kos, M Z; Yan, J; Dick, D M; Agrawal, A; Bucholz, K K; Rice, J P; Johnson, E O; Schuckit, M; Kuperman, S; Kramer, J; Goate, A M; Tischfield, J A; Foroud, T; Nurnberger, J; Hesselbrock, V; Porjesz, B; Bierut, L J; Edenberg, H J; Almasy, L

    2013-07-01

    Alcohol dependence (AD) is a heritable substance addiction with adverse physical and psychological consequences, representing a major health and economic burden on societies worldwide. Genes thus far implicated via linkage, candidate gene and genome-wide association studies (GWAS) account for only a small fraction of its overall risk, with effects varying across ethnic groups. Here we investigate the genetic architecture of alcoholism and report on the extent to which common, genome-wide SNPs collectively account for risk of AD in two US populations, African-Americans (AAs) and European-Americans (EAs). Analyzing GWAS data for two independent case-control sample sets, we compute polymarker scores that are significantly associated with alcoholism (P = 1.64 × 10(-3) and 2.08 × 10(-4) for EAs and AAs, respectively), reflecting the small individual effects of thousands of variants derived from patterns of allelic architecture that are population specific. Simulations show that disease models based on rare and uncommon causal variants (MAF gene location and examined for constituent biological networks, gene enrichment is observed for several cellular processes and functions in both EA and AA populations, transcending their underlying allelic differences. Our results reveal key insights into the complex etiology of AD, raising the possibility of an important role for rare and uncommon variants, and identify polygenic mechanisms that encompass a spectrum of disease liability, with some, such as chloride transporters and glycine metabolism genes, displaying subtle, modifying effects that are likely to escape detection in most GWAS designs.

  2. Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants

    Science.gov (United States)

    Pharoah, Paul D. P.; Michailidou, Kyriaki; Tyrer, Jonathan; Brook, Mark N.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Brown, Judith; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Peto, Julian; dos-Santos-Silva, Isabel; Dudbridge, Frank; Johnson, Nichola; Schmidt, Marjanka K.; Broeks, Annegien; Verhoef, Senno; Rutgers, Emiel J.; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Figueroa, Jonine; Chanock, Stephen J.; Brinton, Louise; Lissowska, Jolanta; Couch, Fergus J.; Olson, Janet E.; Vachon, Celine; Pankratz, Vernon S.; Lambrechts, Diether; Wildiers, Hans; Van Ongeval, Chantal; van Limbergen, Erik; Kristensen, Vessela; Grenaker Alnæs, Grethe; Nord, Silje; Borresen-Dale, Anne-Lise; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Trentham-Dietz, Amy; Newcomb, Polly; Titus, Linda; Egan, Kathleen M.; Hunter, David J.; Lindstrom, Sara; Tamimi, Rulla M.; Kraft, Peter; Rahman, Nazneen; Turnbull, Clare; Renwick, Anthony; Seal, Sheila; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Benitez, Javier; Pilar Zamora, M.; Arias Perez, Jose Ignacio; Menéndez, Primitiva; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Anton-Culver, Hoda; Neuhausen, Susan L.; Ziogas, Argyrios; Bernstein, Leslie; Devilee, Peter; Tollenaar, Robert A. E. M.; Seynaeve, Caroline; van Asperen, Christi J.; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Khusnutdinova, Elza; Bermisheva, Marina; Prokofyeva, Darya; Takhirova, Zalina; Meindl, Alfons; Schmutzler, Rita K.; Sutter, Christian; Yang, Rongxi; Schürmann, Peter; Bremer, Michael; Christiansen, Hans; Park-Simon, Tjoung-Won; Hillemanns, Peter; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Pensotti, Valeria; Hopper, John L.; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C.; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Sigurdson, Alice J.; Doody, Michele M.; Hamann, Ute; Torres, Diana; Ulmer, Hans-Ulrich; Försti, Asta; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Marie Mulligan, Anna; Chenevix-Trench, Georgia; Balleine, Rosemary; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Lindblom, Annika; Margolin, Sara; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Eilber, Ursula; Wang-Gohrke, Shan; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Koppert, Linetta B.; Carpenter, Jane; Clarke, Christine; Scott, Rodney; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Brenner, Hermann; Arndt, Volker; Stegmaier, Christa; Karina Dieffenbach, Aida; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Offit, Kenneth; Vijai, Joseph; Robson, Mark; Rau-Murthy, Rohini; Dwek, Miriam; Swann, Ruth; Annie Perkins, Katherine; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Eccles, Diana M.; Tapper, William J.; Rafiq, Sajjad; John, Esther M.; Whittemore, Alice S.; Slager, Susan; Yannoukakos, Drakoulis; Toland, Amanda E.; Yao, Song; Zheng, Wei; Halverson, Sandra L.; González-Neira, Anna; Pita, Guillermo; Rosario Alonso, M.; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S.; Simard, Jacques; Hall, Per; Easton, Douglas F.; Garcia-Closas, Montserrat

    2015-01-01

    Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report. PMID:25855707

  3. Prediction of breast cancer risk based on profiling with common genetic variants.

    Science.gov (United States)

    Mavaddat, Nasim; Pharoah, Paul D P; Michailidou, Kyriaki; Tyrer, Jonathan; Brook, Mark N; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dunning, Alison M; Shah, Mitul; Luben, Robert; Brown, Judith; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Peto, Julian; Dos-Santos-Silva, Isabel; Dudbridge, Frank; Johnson, Nichola; Schmidt, Marjanka K; Broeks, Annegien; Verhoef, Senno; Rutgers, Emiel J; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J; Figueroa, Jonine; Chanock, Stephen J; Brinton, Louise; Lissowska, Jolanta; Couch, Fergus J; Olson, Janet E; Vachon, Celine; Pankratz, Vernon S; Lambrechts, Diether; Wildiers, Hans; Van Ongeval, Chantal; van Limbergen, Erik; Kristensen, Vessela; Grenaker Alnæs, Grethe; Nord, Silje; Borresen-Dale, Anne-Lise; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Trentham-Dietz, Amy; Newcomb, Polly; Titus, Linda; Egan, Kathleen M; Hunter, David J; Lindstrom, Sara; Tamimi, Rulla M; Kraft, Peter; Rahman, Nazneen; Turnbull, Clare; Renwick, Anthony; Seal, Sheila; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Benitez, Javier; Pilar Zamora, M; Arias Perez, Jose Ignacio; Menéndez, Primitiva; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Anton-Culver, Hoda; Neuhausen, Susan L; Ziogas, Argyrios; Bernstein, Leslie; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; van Asperen, Christi J; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Khusnutdinova, Elza; Bermisheva, Marina; Prokofyeva, Darya; Takhirova, Zalina; Meindl, Alfons; Schmutzler, Rita K; Sutter, Christian; Yang, Rongxi; Schürmann, Peter; Bremer, Michael; Christiansen, Hans; Park-Simon, Tjoung-Won; Hillemanns, Peter; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Pensotti, Valeria; Hopper, John L; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Sigurdson, Alice J; Doody, Michele M; Hamann, Ute; Torres, Diana; Ulmer, Hans-Ulrich; Försti, Asta; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Marie Mulligan, Anna; Chenevix-Trench, Georgia; Balleine, Rosemary; Giles, Graham G; Milne, Roger L; McLean, Catriona; Lindblom, Annika; Margolin, Sara; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Eilber, Ursula; Wang-Gohrke, Shan; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Koppert, Linetta B; Carpenter, Jane; Clarke, Christine; Scott, Rodney; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Brenner, Hermann; Arndt, Volker; Stegmaier, Christa; Karina Dieffenbach, Aida; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Offit, Kenneth; Vijai, Joseph; Robson, Mark; Rau-Murthy, Rohini; Dwek, Miriam; Swann, Ruth; Annie Perkins, Katherine; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Eccles, Diana M; Tapper, William J; Rafiq, Sajjad; John, Esther M; Whittemore, Alice S; Slager, Susan; Yannoukakos, Drakoulis; Toland, Amanda E; Yao, Song; Zheng, Wei; Halverson, Sandra L; González-Neira, Anna; Pita, Guillermo; Rosario Alonso, M; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S; Simard, Jacques; Hall, Per; Easton, Douglas F; Garcia-Closas, Montserrat

    2015-05-01

    Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report. © The Author 2015. Published by Oxford University Press.

  4. Neuroinformatic analyses of common and distinct genetic components associated with major neuropsychiatric disorders.

    Science.gov (United States)

    Lotan, Amit; Fenckova, Michaela; Bralten, Janita; Alttoa, Aet; Dixson, Luanna; Williams, Robert W; van der Voet, Monique

    2014-01-01

    Major neuropsychiatric disorders are highly heritable, with mounting evidence suggesting that these disorders share overlapping sets of molecular and cellular underpinnings. In the current article we systematically test the degree of genetic commonality across six major neuropsychiatric disorders-attention deficit hyperactivity disorder (ADHD), anxiety disorders (Anx), autistic spectrum disorders (ASD), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). We curated a well-vetted list of genes based on large-scale human genetic studies based on the NHGRI catalog of published genome-wide association studies (GWAS). A total of 180 genes were accepted into the analysis on the basis of low but liberal GWAS p-values (NT5C2, PPP1R11, SYNE1, TCF4, TENM4, TRIM26, and ZNRD1. Using a suite of neuroinformatic resources, we showed that many of the shared genes are implicated in the postsynaptic density (PSD), expressed in immune tissues and co-expressed in developing human brain. Using a translational cross-species approach, we detected two distinct genetic components that were both shared by each of the six disorders; the 1st component is involved in CNS development, neural projections and synaptic transmission, while the 2nd is implicated in various cytoplasmic organelles and cellular processes. Combined, these genetic components account for 20-30% of the genetic load. The remaining risk is conferred by distinct, disorder-specific variants. Our systematic comparative analysis of shared and unique genetic factors highlights key gene sets and molecular processes that may ultimately translate into improved diagnosis and treatment of these debilitating disorders.

  5. Assessing Genetic Structure in Common but Ecologically Distinct Carnivores: The Stone Marten and Red Fox.

    Directory of Open Access Journals (Sweden)

    Mafalda P Basto

    Full Text Available The identification of populations and spatial genetic patterns is important for ecological and conservation research, and spatially explicit individual-based methods have been recognised as powerful tools in this context. Mammalian carnivores are intrinsically vulnerable to habitat fragmentation but not much is known about the genetic consequences of fragmentation in common species. Stone martens (Martes foina and red foxes (Vulpes vulpes share a widespread Palearctic distribution and are considered habitat generalists, but in the Iberian Peninsula stone martens tend to occur in higher quality habitats. We compared their genetic structure in Portugal to see if they are consistent with their differences in ecological plasticity, and also to illustrate an approach to explicitly delineate the spatial boundaries of consistently identified genetic units. We analysed microsatellite data using spatial Bayesian clustering methods (implemented in the software BAPS, GENELAND and TESS, a progressive partitioning approach and a multivariate technique (Spatial Principal Components Analysis-sPCA. Three consensus Bayesian clusters were identified for the stone marten. No consensus was achieved for the red fox, but one cluster was the most probable clustering solution. Progressive partitioning and sPCA suggested additional clusters in the stone marten but they were not consistent among methods and were geographically incoherent. The contrasting results between the two species are consistent with the literature reporting stricter ecological requirements of the stone marten in the Iberian Peninsula. The observed genetic structure in the stone marten may have been influenced by landscape features, particularly rivers, and fragmentation. We suggest that an approach based on a consensus clustering solution of multiple different algorithms may provide an objective and effective means to delineate potential boundaries of inferred subpopulations. sPCA and progressive

  6. Common genetic variants and modification of penetrance of BRCA2-associated breast cancer.

    Directory of Open Access Journals (Sweden)

    Mia M Gaudet

    2010-10-01

    Full Text Available The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5 and 39 SNPs had p-values<10(-4. These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499 and chromosome 10 (rs16917302. The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR and 95% confidence intervals (CI for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, and for rs311499 was 0.72 (95% CI 0.61-0.85, . FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, . These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.

  7. Common genetic variants and modification of penetrance of BRCA2-associated breast cancer.

    Science.gov (United States)

    Gaudet, Mia M; Kirchhoff, Tomas; Green, Todd; Vijai, Joseph; Korn, Joshua M; Guiducci, Candace; Segrè, Ayellet V; McGee, Kate; McGuffog, Lesley; Kartsonaki, Christiana; Morrison, Jonathan; Healey, Sue; Sinilnikova, Olga M; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Gauthier-Villars, Marion; Sobol, Hagay; Longy, Michel; Frenay, Marc; GEMO Study Collaborators; Hogervorst, Frans B L; Rookus, Matti A; Collée, J Margriet; Hoogerbrugge, Nicoline; van Roozendaal, Kees E P; Piedmonte, Marion; Rubinstein, Wendy; Nerenstone, Stacy; Van Le, Linda; Blank, Stephanie V; Caldés, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Lazaro, Conxi; Blanco, Ignacio; Arason, Adalgeir; Johannsson, Oskar T; Barkardottir, Rosa B; Devilee, Peter; Olopade, Olofunmilayo I; Neuhausen, Susan L; Wang, Xianshu; Fredericksen, Zachary S; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Viel, Alessandra; Radice, Paolo; Phelan, Catherine M; Narod, Steven; Rennert, Gad; Lejbkowicz, Flavio; Flugelman, Anath; Andrulis, Irene L; Glendon, Gord; Ozcelik, Hilmi; Toland, Amanda E; Montagna, Marco; D'Andrea, Emma; Friedman, Eitan; Laitman, Yael; Borg, Ake; Beattie, Mary; Ramus, Susan J; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Tim; Spurdle, Amanda B; Chen, Xiaoqing; Holland, Helene; John, Esther M; Hopper, John L; Buys, Saundra S; Daly, Mary B; Southey, Melissa C; Terry, Mary Beth; Tung, Nadine; Overeem Hansen, Thomas V; Nielsen, Finn C; Greene, Mark H; Greene, Mark I; Mai, Phuong L; Osorio, Ana; Durán, Mercedes; Andres, Raquel; Benítez, Javier; Weitzel, Jeffrey N; Garber, Judy; Hamann, Ute; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Platte, Radka; Evans, D Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Walker, Lisa; Eason, Jacqueline; Barwell, Julian; Godwin, Andrew K; Schmutzler, Rita K; Wappenschmidt, Barbara; Engert, Stefanie; Arnold, Norbert; Gadzicki, Dorothea; Dean, Michael; Gold, Bert; Klein, Robert J; Couch, Fergus J; Chenevix-Trench, Georgia; Easton, Douglas F; Daly, Mark J; Antoniou, Antonis C; Altshuler, David M; Offit, Kenneth

    2010-10-28

    The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5) and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, ) and for rs311499 was 0.72 (95% CI 0.61-0.85, ). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, ). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.

  8. Common genetic variants and modification of penetrance of BRCA2-associated breast cancer.

    Directory of Open Access Journals (Sweden)

    Mia M Gaudet

    2010-10-01

    Full Text Available The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5 and 39 SNPs had p-values<10(-4. These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499 and chromosome 10 (rs16917302. The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR and 95% confidence intervals (CI for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, and for rs311499 was 0.72 (95% CI 0.61-0.85, . FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, . These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.

  9. Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer

    Science.gov (United States)

    Guiducci, Candace; Segrè, Ayellet V.; McGee, Kate; McGuffog, Lesley; Kartsonaki, Christiana; Morrison, Jonathan; Healey, Sue; Sinilnikova, Olga M.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Gauthier-Villars, Marion; Sobol, Hagay; Longy, Michel; Frenay, Marc; GEMO Study Collaborators; Hogervorst, Frans B. L.; Rookus, Matti A.; Collée, J. Margriet; Hoogerbrugge, Nicoline; van Roozendaal, Kees E. P.; Piedmonte, Marion; Rubinstein, Wendy; Nerenstone, Stacy; Van Le, Linda; Blank, Stephanie V.; Caldés, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Lazaro, Conxi; Blanco, Ignacio; Arason, Adalgeir; Johannsson, Oskar T.; Barkardottir, Rosa B.; Devilee, Peter; Olopade, Olofunmilayo I.; Neuhausen, Susan L.; Wang, Xianshu; Fredericksen, Zachary S.; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Viel, Alessandra; Radice, Paolo; Phelan, Catherine M.; Narod, Steven; Rennert, Gad; Lejbkowicz, Flavio; Flugelman, Anath; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Toland, Amanda E.; Montagna, Marco; D'Andrea, Emma; Friedman, Eitan; Laitman, Yael; Borg, Ake; Beattie, Mary; Ramus, Susan J.; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Tim; Spurdle, Amanda B.; Chen, Xiaoqing; Holland, Helene; John, Esther M.; Hopper, John L.; Buys, Saundra S.; Daly, Mary B.; Southey, Melissa C.; Terry, Mary Beth; Tung, Nadine; Overeem Hansen, Thomas V.; Nielsen, Finn C.; Greene, Mark I.; Mai, Phuong L.; Osorio, Ana; Durán, Mercedes; Andres, Raquel; Benítez, Javier; Weitzel, Jeffrey N.; Garber, Judy; Hamann, Ute; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Platte, Radka; Evans, D. Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Walker, Lisa; Eason, Jacqueline; Barwell, Julian; Godwin, Andrew K.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engert, Stefanie; Arnold, Norbert; Gadzicki, Dorothea; Dean, Michael; Gold, Bert; Klein, Robert J.; Couch, Fergus J.; Chenevix-Trench, Georgia; Easton, Douglas F.; Daly, Mark J.; Antoniou, Antonis C.; Altshuler, David M.; Offit, Kenneth

    2010-01-01

    The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10−5 and 39 SNPs had p-values<10−4. These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66–0.86, ) and for rs311499 was 0.72 (95% CI 0.61–0.85, ). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18–1.39, ). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer. PMID:21060860

  10. Comparative transcriptome analysis reveals the genetic basis of skin color variation in common carp.

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    Yanliang Jiang

    Full Text Available The common carp is an important aquaculture species that is widely distributed across the world. During the long history of carp domestication, numerous carp strains with diverse skin colors have been established. Skin color is used as a visual criterion to determine the market value of carp. However, the genetic basis of common carp skin color has not been extensively studied.In this study, we performed Illumina sequencing on two common carp strains: the reddish Xingguo red carp and the brownish-black Yellow River carp. A total of 435,348,868 reads were generated, resulting in 198,781 assembled contigs that were used as reference sequences. Comparisons of skin transcriptome files revealed 2,012 unigenes with significantly different expression in the two common carp strains, including 874 genes that were up-regulated in Xingguo red carp and 1,138 genes that were up-regulated in Yellow River carp. The expression patterns of 20 randomly selected differentially expressed genes were validated using quantitative RT-PCR. Gene pathway analysis of the differentially expressed genes indicated that melanin biosynthesis, along with the Wnt and MAPK signaling pathways, is highly likely to affect the skin pigmentation process. Several key genes involved in the skin pigmentation process, including TYRP1, SILV, ASIP and xCT, showed significant differences in their expression patterns between the two strains.In this study, we conducted a comparative transcriptome analysis of Xingguo red carp and Yellow River carp skins, and we detected key genes involved in the common carp skin pigmentation process. We propose that common carp skin pigmentation depends upon at least three pathways. Understanding fish skin color genetics will facilitate future molecular selection of the fish skin colors with high market values.

  11. Comparative Transcriptome Analysis Reveals the Genetic Basis of Skin Color Variation in Common Carp

    Science.gov (United States)

    Jiang, Yanliang; Zhang, Songhao; Xu, Jian; Feng, Jianxin; Mahboob, Shahid; Al-Ghanim, Khalid A.; Sun, Xiaowen; Xu, Peng

    2014-01-01

    Background The common carp is an important aquaculture species that is widely distributed across the world. During the long history of carp domestication, numerous carp strains with diverse skin colors have been established. Skin color is used as a visual criterion to determine the market value of carp. However, the genetic basis of common carp skin color has not been extensively studied. Methodology/Principal Findings In this study, we performed Illumina sequencing on two common carp strains: the reddish Xingguo red carp and the brownish-black Yellow River carp. A total of 435,348,868 reads were generated, resulting in 198,781 assembled contigs that were used as reference sequences. Comparisons of skin transcriptome files revealed 2,012 unigenes with significantly different expression in the two common carp strains, including 874 genes that were up-regulated in Xingguo red carp and 1,138 genes that were up-regulated in Yellow River carp. The expression patterns of 20 randomly selected differentially expressed genes were validated using quantitative RT-PCR. Gene pathway analysis of the differentially expressed genes indicated that melanin biosynthesis, along with the Wnt and MAPK signaling pathways, is highly likely to affect the skin pigmentation process. Several key genes involved in the skin pigmentation process, including TYRP1, SILV, ASIP and xCT, showed significant differences in their expression patterns between the two strains. Conclusions In this study, we conducted a comparative transcriptome analysis of Xingguo red carp and Yellow River carp skins, and we detected key genes involved in the common carp skin pigmentation process. We propose that common carp skin pigmentation depends upon at least three pathways. Understanding fish skin color genetics will facilitate future molecular selection of the fish skin colors with high market values. PMID:25255374

  12. Heritability estimates of the Big Five personality traits based on common genetic variants.

    Science.gov (United States)

    Power, R A; Pluess, M

    2015-07-14

    According to twin studies, the Big Five personality traits have substantial heritable components explaining 40-60% of the variance, but identification of associated genetic variants has remained elusive. Consequently, knowledge regarding the molecular genetic architecture of personality and to what extent it is shared across the different personality traits is limited. Using genomic-relatedness-matrix residual maximum likelihood analysis (GREML), we here estimated the heritability of the Big Five personality factors (extraversion, agreeableness, conscientiousness, neuroticism and openness for experience) in a sample of 5011 European adults from 527,469 single-nucleotide polymorphisms across the genome. We tested for the heritability of each personality trait, as well as for the genetic overlap between the personality factors. We found significant and substantial heritability estimates for neuroticism (15%, s.e. = 0.08, P = 0.04) and openness (21%, s.e. = 0.08, P agreeableness and conscientiousness. The bivariate analyses showed that the variance explained by common variants entirely overlapped between neuroticism and openness (rG = 1.00, P personality traits using the GREML approach. Findings should be considered exploratory and suggest that detectable heritability estimates based on common variants is shared between neuroticism and openness to experiences.

  13. Common genetic variants in Wnt signaling pathway genes as potential prognostic biomarkers for colorectal cancer.

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    Wen-Chien Ting

    Full Text Available Compelling evidence has implicated the Wnt signaling pathway in the pathogenesis of colorectal cancer. We assessed the use of tag single nucleotide polymorphisms (tSNPs in adenomatous polyposis coli (APC/β-catenin (CTNNB1 genes to predict outcomes in patients with colorectal cancer. We selected and genotyped 10 tSNP to predict common variants across entire APC and CTNNB1 genes in 282 colorectal cancer patients. The associations of these tSNPs with distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier analysis, Cox regression model, and survival tree analysis. The 5-year overall survival rate was 68.3%. Survival tree analysis identified a higher-order genetic interaction profile consisting of the APC rs565453, CTNNB1 2293303, and APC rs1816769 that was significantly associated with overall survival. The 5-year survival overall rates were 89.2%, 66.1%, and 58.8% for the low-, medium-, and high-risk genetic profiles, respectively (log-rank P = 0.001. After adjusting for possible confounders, including age, gender, carcinoembryonic antigen levels, tumor differentiation, stage, lymphovascular invasion, perineural invasion, and lymph node involvement, the genetic interaction profile remained significant. None of the studied SNPs were individually associated with distant metastasis-free survival and overall survival. Our results suggest that the genetic interaction profile among Wnt pathway SNPs might potentially increase the prognostic value in outcome prediction for colorectal cancer.

  14. Mean Platelet Volume and Arterial Stiffness – Clinical Relationship and Common Genetic Variability

    Science.gov (United States)

    Panova-Noeva, Marina; Arnold, Natalie; Hermanns, M. Iris; Prochaska, Jürgen H.; Schulz, Andreas; Spronk, Henri M.; Binder, Harald; Pfeiffer, Norbert; Beutel, Manfred; Blankenberg, Stefan; Zeller, Tanja; Lotz, Johannes; Münzel, Thomas; Lackner, Karl J.; ten Cate, Hugo; Wild, Philipp S.

    2017-01-01

    Vessel wall stiffening is an important clinical parameter, but it is unknown whether platelets, key elements in the pathogenesis of arterial thrombosis, are associated with arterial stiffness. The present studies sought to determine whether mean platelet volume (MPV), a potential marker of platelet activation, is linked to vascular elasticity as assessed by the augmentation index (AIx), in 15,010 individuals from the population-based Gutenberg Health Study. Multivariable analysis showed that MPV in both males (β 0.776; 95thCI [0.250;1.16]; p = 0.0024) and females (β 0.881[0.328;1.43]; p = 0.0018) is strongly associated with AIx. Individuals with MPV and AIx above the sex-specific medians had worse survival. Association analysis between MPV-related genetic variants and arterial stiffness identified four genetic variants in males and one in females related with AIx. Cox regression analysis for mortality identified one of these joint genetic variants close to ring finger protein 145 gene (RNF145, rs10076782) linked with increased mortality (hazard ratio 2.02; 95thCI [1.35;3.02]; p = 0.00061). Thus, these population-based data demonstrate a close relation between platelet volume as a potential marker of platelet activation and arterial stiffness in both sexes. Further research is warranted to further elucidate the mechanisms underlying larger platelets‘ role in arterial stiffening including the role of shared common genetics. PMID:28059166

  15. A common genetic influence on human intensity ratings of sugars and high-potency sweeteners.

    Science.gov (United States)

    Hwang, Liang-Dar; Zhu, Gu; Breslin, Paul A S; Reed, Danielle R; Martin, Nicholas G; Wright, Margaret J

    2015-08-01

    The perception of sweetness varies among individuals but the sources of this variation are not fully understood. Here, in a sample of 1,901 adolescent and young adults (53.8% female; 243 MZ and 452 DZ twin pairs, 511 unpaired individuals; mean age 16.2±2.8, range 12–26 years), we studied the variation in the perception of sweetness intensity of two monosaccharides and two high-potency sweeteners: glucose, fructose, neohesperidine dihydrochalcone (NHDC), and aspartame. Perceived intensity for all sweeteners decreased with age (2–5% per year) and increased with the history of otitis media (6–9%). Males rated aspartame slightly stronger than females (7%). We found similar heritabilities for sugars (glucose: h2=0.31, fructose: h2=0.34) and high-potency sweeteners (NHDC: h2=0.31, aspartame: h2=0.30); all were in the modest range. Multivariate modeling showed that a common genetic factor accounted for >75% of the genetic variance in the four sweeteners, suggesting that individual differences in perceived sweet intensity, which are partly due to genetic factors, may be attributed to a single set of genes. This study provided evidence of the shared genetic pathways between the perception of sugars and high-potency sweeteners.

  16. Identification of common genetic modifiers of neurodegenerative diseases from an integrative analysis of diverse genetic screens in model organisms

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    Chen Xi

    2012-02-01

    Full Text Available Abstract Background An array of experimental models have been developed in the small model organisms C. elegans, S. cerevisiae and D. melanogaster for the study of various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and expanded polyglutamine diseases as exemplified by Huntington's disease (HD and related ataxias. Genetic approaches to determine the nature of regulators of the disease phenotypes have ranged from small scale to essentially whole genome screens. The published data covers distinct models in all three organisms and one important question is the extent to which shared genetic factors can be uncovered that affect several or all disease models. Surprisingly it has appeared that there may be relatively little overlap and that many of the regulators may be organism or disease-specific. There is, however, a need for a fully integrated analysis of the available genetic data based on careful comparison of orthologues across the species to determine the real extent of overlap. Results We carried out an integrated analysis using C. elegans as the baseline model organism since this is the most widely studied in this context. Combination of data from 28 published studies using small to large scale screens in all three small model organisms gave a total of 950 identifications of genetic regulators. Of these 624 were separate genes with orthologues in C. elegans. In addition, 34 of these genes, which all had human orthologues, were found to overlap across studies. Of the common genetic regulators some such as chaperones, ubiquitin-related enzymes (including the E3 ligase CHIP which directly links the two pathways and histone deacetylases were involved in expected pathways whereas others such as the peroxisomal acyl CoA-oxidase suggest novel targets for neurodegenerative disease therapy Conclusions We identified a significant number of overlapping regulators of neurodegenerative disease models. Since the diseases

  17. Genetic progress and potential of common bean families obtained by recurrent selection

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    Anatércia Ferreira Alves

    2015-12-01

    Full Text Available The objective of this study was to estimate the genetic gain of two recurrent selection cycles in common bean breeding and identify families with the potential to generate superior lines. The base population, cycle zero (C0, was obtained by combining 20 carioca bean parents, populations with favorable phenotypes for several agronomically important traits. The parents were recombined in a circulant diallel scheme, in which each parent participated in two crosses, generating 20 populations. From these populations, families were derived and evaluated for three seasons in the generations F2:3, F2:4 and F2:5. The same procedures of recombination and evaluation in C0 were performed in cycle one (CI. The genetic gain for yield, estimated from the simultaneous evaluation of the 40 best families of each cycle, was 8.6%. Families with potential to generate superior lines to cultivar Pérola were identified, especially among the CI families.

  18. Breast cancer predisposition and brain hemispheric laterality specification likely share a common genetic cause.

    Science.gov (United States)

    Klar, Amar J S

    2011-01-01

    The majority of breast cancer cases seen in women remain unexplained by simple Mendelian genetics. It is generally hypothesized that such non-familial, so-called sporadic cases, result from exposure of the affected individuals to a cancer-causing environment and/or from stochastic cell biological errors. Clearly, adverse environment exposure can cause disease, but is that necessarily the cause of most sporadic cases? Curiously, female breast cancer patients who were selected to prefer right-hand-use reportedly exhibited a higher incidence of reversed-brain hemispheric laterality when compared to that of the public at large. Notably, such a higher level of hemispheric reversal is also found in healthy, left-handed or ambidextrous persons. Based on the association between these disparate traits, a new hypothesis for the etiology of sporadic breast cancer cases is advanced here; breast cancer predisposition and brain laterality development likely share a common genetic cause.

  19. Potential International Approaches to Ownership/Control of Human Genetic Resources.

    Science.gov (United States)

    Rhodes, Catherine

    2016-09-01

    In its governance activities for genetic resources, the international community has adopted various approaches to their ownership, including: free access; common heritage of mankind; intellectual property rights; and state sovereign rights. They have also created systems which combine elements of these approaches. While governance of plant and animal genetic resources is well-established internationally, there has not yet been a clear approach selected for human genetic resources. Based on assessment of the goals which international governance of human genetic resources ought to serve, and the implications for how they will be accessed and utilised, it is argued that common heritage of mankind will be the most appropriate approach to adopt to their ownership/control. It does this with the aim of stimulating discussion in this area and providing a starting point for deeper consideration of how a common heritage of mankind, or similar, regime for human genetic resources would function and be implemented.

  20. Multiobjective Genetic Algorithm applied to dengue control.

    Science.gov (United States)

    Florentino, Helenice O; Cantane, Daniela R; Santos, Fernando L P; Bannwart, Bettina F

    2014-12-01

    Dengue fever is an infectious disease caused by a virus of the Flaviridae family and transmitted to the person by a mosquito of the genus Aedes aegypti. This disease has been a global public health problem because a single mosquito can infect up to 300 people and between 50 and 100 million people are infected annually on all continents. Thus, dengue fever is currently a subject of research, whether in the search for vaccines and treatments for the disease or efficient and economical forms of mosquito control. The current study aims to study techniques of multiobjective optimization to assist in solving problems involving the control of the mosquito that transmits dengue fever. The population dynamics of the mosquito is studied in order to understand the epidemic phenomenon and suggest strategies of multiobjective programming for mosquito control. A Multiobjective Genetic Algorithm (MGA_DENGUE) is proposed to solve the optimization model treated here and we discuss the computational results obtained from the application of this technique.

  1. Genetic variability for iron and zinc content in common bean lines and interaction with water availability.

    Science.gov (United States)

    Pereira, H S; Del Peloso, M J; Bassinello, P Z; Guimarães, C M; Melo, L C; Faria, L C

    2014-08-28

    The common bean is an important source of iron and zinc in humans. Increases in the contents of these minerals can combat mineral deficiencies, but these contents are influenced by environmental conditions. Thus, the objectives of this study were to investigate the interaction between common bean lines and water availability on iron and zinc contents (CFe and CZn, respectively), identify superior lines with stable CFe and CZn, and test for a genetic relationship between CFe and CZn. Six crop trials were performed using a randomized block design with three replications. The trials were performed during the winter sowing period for three different combinations of year and site in Brazil. For each combination, 53 lines were evaluated across two parallel trials; one trial was irrigated according to the crop requirements, and the other trial operated under a water deficit. Interaction was detected between lines and environments, and between lines and water availability for CFe and CZn. However, some lines exhibited high CFe and CZn in both conditions. Lines G 6492 and G 6490 exhibited high mean values, stability, and adaptability for both minerals. Other lines exhibited high CFe (Xamego) or CZn (Bambuí and Iapar 65). A moderate genetic correlation (0.62) between CFe and CZn was detected. Water availability during the common bean cycle had an effect on CFe and CZn; however, lines with high CFe and CZn in different conditions of water availability and environment were detected.

  2. Genetic control of mosquitoes: population suppression strategies.

    Science.gov (United States)

    Wilke, André Barretto Bruno; Marrelli, Mauro Toledo

    2012-01-01

    Over the last two decades, morbidity and mortality from malaria and dengue fever among other pathogens are an increasing Public Health problem. The increase in the geographic distribution of vectors is accompanied by the emergence of viruses and diseases in new areas. There are insufficient specific therapeutic drugs available and there are no reliable vaccines for malaria or dengue, although some progress has been achieved, there is still a long way between its development and actual field use. Most mosquito control measures have failed to achieve their goals, mostly because of the mosquito's great reproductive capacity and genomic flexibility. Chemical control is increasingly restricted due to potential human toxicity, mortality in no target organisms, insecticide resistance, and other environmental impacts. Other strategies for mosquito control are desperately needed. The Sterile Insect Technique (SIT) is a species-specific and environmentally benign method for insect population suppression, it is based on mass rearing, radiation mediated sterilization, and release of a large number of male insects. Releasing of Insects carrying a dominant lethal gene (RIDL) offers a solution to many of the drawbacks of traditional SIT that have limited its application in mosquitoes while maintaining its environmentally friendly and species-specific utility. The self-limiting nature of sterile mosquitoes tends to make the issues related to field use of these somewhat less challenging than for self-spreading systems characteristic of population replacement strategies. They also are closer to field use, so might be appropriate to consider first. The prospect of genetic control methods against mosquito vectored human diseases is rapidly becoming a reality, many decisions will need to be made on a national, regional and international level regarding the biosafety, social, cultural and ethical aspects of the use and deployment of these vector control methods.

  3. Genetic Control of Mosquitoes: population suppression strategies

    Directory of Open Access Journals (Sweden)

    André Barretto Bruno Wilke

    2012-10-01

    Full Text Available Over the last two decades, morbidity and mortality from malaria and dengue fever among other pathogens are an increasing Public Health problem. The increase in the geographic distribution of vectors is accompanied by the emergence of viruses and diseases in new areas. There are insufficient specific therapeutic drugs available and there are no reliable vaccines for malaria or dengue, although some progress has been achieved, there is still a long way between its development and actual field use. Most mosquito control measures have failed to achieve their goals, mostly because of the mosquito's great reproductive capacity and genomic flexibility. Chemical control is increasingly restricted due to potential human toxicity, mortality in no target organisms, insecticide resistance, and other environmental impacts. Other strategies for mosquito control are desperately needed. The Sterile Insect Technique (SIT is a species-specific and environmentally benign method for insect population suppression, it is based on mass rearing, radiation mediated sterilization, and release of a large number of male insects. Releasing of Insects carrying a dominant lethal gene (RIDL offers a solution to many of the drawbacks of traditional SIT that have limited its application in mosquitoes while maintaining its environmentally friendly and species-specific utility. The self-limiting nature of sterile mosquitoes tends to make the issues related to field use of these somewhat less challenging than for self-spreading systems characteristic of population replacement strategies. They also are closer to field use, so might be appropriate to consider first. The prospect of genetic control methods against mosquito vectored human diseases is rapidly becoming a reality, many decisions will need to be made on a national, regional and international level regarding the biosafety, social, cultural and ethical aspects of the use and deployment of these vector control methods.

  4. Common genetic variants associated with thyroid function may be risk alleles for Hashimoto's disease and Graves' disease.

    Science.gov (United States)

    Campbell, Purdey; Brix, Thomas H; Wilson, Scott G; Ward, Lynley C; Hui, Jennie; Beilby, John P; Hegedüs, Laszlo; Walsh, John P

    2015-02-14

    Recent studies have identified common genetic variants associated with TSH, free T4 and thyroid peroxidase antibodies, but it is unclear whether these differ between patients with Hashimoto's disease and Graves' disease. To examine whether 11 common genetic variants differ between Graves' disease and Hashimoto's disease. We genotyped 11 common variants in a discovery cohort of 203 Australian patients with autoimmune thyroid disease (AITD). Two variants with significant or suggestive associations were analysed in a replication cohort of 384 Danish patients. For rs753760 (PDE10A), the minor allele frequency in Graves' disease and Hashimoto's disease was 0·38 vs. 0·23, respectively, (P = 6·42 × 10(-4) ) in the discovery cohort, 0·29 vs. 0·24 (P = 0·147) in the replication cohort and 0·32 vs. 0·24 in combined analysis (P = 0·0021; all analyses adjusted for sex). In healthy controls from Busselton, the frequency was 0·29, significantly different from Hashimoto's disease but not Graves' disease. For rs4889009 (MAF gene region), the frequency of the minor G-allele in Graves' disease and Hashimoto's disease was 0·48 vs. 0·36 (P = 0·0156) in the discovery cohort, 0·48 vs. 0·34 (P = 1·83 × 10(-4) ) in the replication cohort and 0·48 vs. 0·35 in the combined analysis (P = 7·53 × 10(-6) ); in controls, the frequency was 0·38, significantly different from Graves' disease but not Hashimoto's disease. After further adjustment for smoking, associations with rs4889009 remained significant, whereas those with rs753760 were not. Common variants in PDE10A and MAF gene regions may influence whether patients with AITD develop Graves' disease or Hashimoto's disease. © 2015 John Wiley & Sons Ltd.

  5. Common genetic variation in the Estrogen Receptor Beta (ESR2 gene and osteoarthritis: results of a meta-analysis

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    Rivadeneira Fernando

    2010-11-01

    Full Text Available Abstract Background The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis. Methods In the discovery study, the Rotterdam Study-I, 7 single nucleotide polymorphisms (SNPs were genotyped and tested for association with hip (284 cases, 2772 controls, knee (665 cases, 2075 controls, and hand OA (874 cases, 2184 controls using an additive model. In the replication stage one SNP (rs1256031 was tested in an additional 2080 hip, 1318 knee and 557 hand OA cases and 4001, 2631 and 1699 controls respectively. Fixed- and random-effects meta-analyses were performed over the complete dataset including 2364 hip, 1983 knee and 1431 hand OA cases and approximately 6000 controls. Results The C allele of rs1256031 was associated with a 36% increased odds of hip OA in women of the Rotterdam Study-I (OR 1.36, 95% CI 1.08-1.70, p = 0.009. Haplotype analysis and analysis of knee- and hand OA did not give additional information. With the replication studies, the meta-analysis did not show a significant effect of this SNP on hip OA in the total population (OR 1.06, 95% CI 0.99-1.15, p = 0.10. Stratification according to gender did not change the results. In this study, we had 80% power to detect an odds ratio of at least 1.14 for hip OA (α = 0.05. Conclusion This study showed that common genetic variation in the ESR2 gene is not likely to influence the risk of osteoarthritis with effects smaller than a 13% increase.

  6. Genetics and Genomics of Single-Gene Cardiovascular Diseases: Common Hereditary Cardiomyopathies as Prototypes of Single-Gene Disorders.

    Science.gov (United States)

    Marian, Ali J; van Rooij, Eva; Roberts, Robert

    2016-12-27

    This is the first of 2 review papers on genetics and genomics appearing as part of the series on "omics." Genomics pertains to all components of an organism's genes, whereas genetics involves analysis of a specific gene or genes in the context of heredity. The paper provides introductory comments, describes the basis of human genetic diversity, and addresses the phenotypic consequences of genetic variants. Rare variants with large effect sizes are responsible for single-gene disorders, whereas complex polygenic diseases are typically due to multiple genetic variants, each exerting a modest effect size. To illustrate the clinical implications of genetic variants with large effect sizes, 3 common forms of hereditary cardiomyopathies are discussed as prototypic examples of single-gene disorders, including their genetics, clinical manifestations, pathogenesis, and treatment. The genetic basis of complex traits is discussed in a separate paper. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  7. Can genetic pleiotropy replicate common clinical constellations of cardiovascular disease and risk?

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    Omri Gottesman

    Full Text Available The relationship between obesity, diabetes, hyperlipidemia, hypertension, kidney disease and cardiovascular disease (CVD is established when looked at from a clinical, epidemiological or pathophysiological perspective. Yet, when viewed from a genetic perspective, there is comparatively little data synthesis that these conditions have an underlying relationship. We sought to investigate the overlap of genetic variants independently associated with each of these commonly co-existing conditions from the NHGRI genome-wide association study (GWAS catalog, in an attempt to replicate the established notion of shared pathophysiology and risk. We used pathway-based analyses to detect subsets of pleiotropic genes involved in similar biological processes. We identified 107 eligible GWAS studies related to CVD and its established comorbidities and risk factors and assigned genes that correspond to the associated signals based on their position. We found 44 positional genes shared across at least two CVD-related phenotypes that independently recreated the established relationship between the six phenotypes, but only if studies representing non-European populations were included. Seven genes revealed pleiotropy across three or more phenotypes, mostly related to lipid transport and metabolism. Yet, many genes had no relationship to each other or to genes with established functional connection. Whilst we successfully reproduced established relationships between CVD risk factors using GWAS findings, interpretation of biological pathways involved in the observed pleiotropy was limited. Further studies linking genetic variation to gene expression, as well as describing novel biological pathways will be needed to take full advantage of GWAS results.

  8. The mGA1.0: A common LISP implementation of a messy genetic algorithm

    Science.gov (United States)

    Goldberg, David E.; Kerzic, Travis

    1990-01-01

    Genetic algorithms (GAs) are finding increased application in difficult search, optimization, and machine learning problems in science and engineering. Increasing demands are being placed on algorithm performance, and the remaining challenges of genetic algorithm theory and practice are becoming increasingly unavoidable. Perhaps the most difficult of these challenges is the so-called linkage problem. Messy GAs were created to overcome the linkage problem of simple genetic algorithms by combining variable-length strings, gene expression, messy operators, and a nonhomogeneous phasing of evolutionary processing. Results on a number of difficult deceptive test functions are encouraging with the mGA always finding global optima in a polynomial number of function evaluations. Theoretical and empirical studies are continuing, and a first version of a messy GA is ready for testing by others. A Common LISP implementation called mGA1.0 is documented and related to the basic principles and operators developed by Goldberg et. al. (1989, 1990). Although the code was prepared with care, it is not a general-purpose code, only a research version. Important data structures and global variations are described. Thereafter brief function descriptions are given, and sample input data are presented together with sample program output. A source listing with comments is also included.

  9. Development and use of genetically uniform strains of common carp in experimental animal research.

    Science.gov (United States)

    Bongers, A B; Sukkel, M; Gort, G; Komen, J; Richter, C J

    1998-10-01

    Fish are widely used in numerous fields of basic and applied research. Currently, they are the third laboratory animal group in numbers, and will become increasingly important. Common carp is a major species in both aquaculture and research. Inbred strains of carp by gynogenetic (only female inheritance) and androgenetic (only male inheritance) reproduction techniques were developed at our university. With these methods, homozygous animals are produced in one generation and we present the production of homozygous inbred and F1 hybrid strains of common carp. As in mammalian research, using genetically well defined fish is a methodological necessity since in outbred stocks: (1) repeatability between experiments is low, (2) high levels of inbreeding may have accumulated and (3) high intrastrain variability might obscure treatment effects. Within inbred strains, the variation is reduced and as a result, less animals (compared to outbreds) are necessary to obtain statistically significant results. We illustrate this with experimental data from an F1 hybrid and partly outbred strain of common carp, both subjected to an antibiotic treatment resulting in reduced gonadal growth. Results obtained from a single inbred strain should be generalized with the use of a panel of inbred strains. We show that optimal allocation of animals between and within inbred strains depends on the ratio (variation between strains): (variation within strains). When selecting a panel of inbred strains, attention has to be paid to genetic relations between strains to avoid testing within a limited genetic range. It should be considered that in inbred strains, (genic) dominance and interaction effects are absent, due to the absence of heterozygous genotypes. In general, variation within inbred strains will be reduced for traits with a high degree of genetic determination. However, in inbred strains of carp produced by gynogenesis or androgenesis, the chromosome manipulation treatment induces

  10. Genetic noise control via protein oligomerization

    Energy Technology Data Exchange (ETDEWEB)

    Ghim, C; Almaas, E

    2008-06-12

    Gene expression in a cell entails random reaction events occurring over disparate time scales. Thus, molecular noise that often results in phenotypic and population-dynamic consequences sets a fundamental limit to biochemical signaling. While there have been numerous studies correlating the architecture of cellular reaction networks with noise tolerance, only a limited effort has been made to understand the dynamical role of protein-protein associations. We have developed a fully stochastic model for the positive feedback control of a single gene, as well as a pair of genes (toggle switch), integrating quantitative results from previous in vivo and in vitro studies. In particular, we explicitly account for the fast protein binding-unbinding kinetics, RNA polymerases, and the promoter/operator sequences of DNA. We find that the overall noise-level is reduced and the frequency content of the noise is dramatically shifted to the physiologically irrelevant high-frequency regime in the presence of protein dimerization. This is independent of the choice of monomer or dimer as transcription factor and persists throughout the multiple model topologies considered. For the toggle switch, we additionally find that the presence of a protein dimer, either homodimer or heterodimer, may significantly reduce its intrinsic switching rate. Hence, the dimer promotes the robust function of bistable switches by preventing the uninduced (induced) state from randomly being induced (uninduced). The specific binding between regulatory proteins provides a buffer that may prevent the propagation of fluctuations in genetic activity. The capacity of the buffer is a non-monotonic function of association-dissociation rates. Since the protein oligomerization per se does not require extra protein components to be expressed, it provides a basis for the rapid control of intrinsic or extrinsic noise. The stabilization of phenotypically important toggle switches, and nested positive feedback loops in

  11. Abandoning the common law: medical negligence, genetic tests and wrongful life in the Australian High Court.

    Science.gov (United States)

    Faunce, Thomas; Jefferys, Susannah

    2007-05-01

    The Australian High Court recently found that the common law could allow parents to claim tortious damages when medical negligence was proven to have led to the birth of an unplanned, but healthy, baby (Cattanach v Melchior (2003) 215 CLR 1). In Harriton v Stephens (2006) 80 ALJR 791; [2006] HCA 15 and Waller v James; Waller v Hoolahan (2006) 80 ALJR 846; [2006] HCA 16 the High Court in a six-to-one decision (Kirby J dissenting) decided that no such claim could be made by a child when medical negligence in failing to order an in utero genetic test caused the child severe disability. In an era when almost all pregnancies will soon require patented fetal genetic tests as part of the professional standard of care, the High Court, by barring so-called "wrongful life" (better termed "wrongful suffering") claims, may have created a partial immunity from suit for their corporate manufacturers and the doctors who administer them. What lessons can be learnt from this case about how the Australian High Court is, or should be, approaching medical negligence cases and its role as guardian of the Australian common law?

  12. Genetic evidence for common pathways in human age-related diseases.

    Science.gov (United States)

    Johnson, Simon C; Dong, Xiao; Vijg, Jan; Suh, Yousin

    2015-10-01

    Aging is the single largest risk factor for chronic disease. Studies in model organisms have identified conserved pathways that modulate aging rate and the onset and progression of multiple age-related diseases, suggesting that common pathways of aging may influence age-related diseases in humans as well. To determine whether there is genetic evidence supporting the notion of common pathways underlying age-related diseases, we analyzed the genes and pathways found to be associated with five major categories of age-related disease using a total of 410 genomewide association studies (GWAS). While only a small number of genes are shared among all five disease categories, those found in at least three of the five major age-related disease categories are highly enriched for apoliprotein metabolism genes. We found that a more substantial number of gene ontology (GO) terms are shared among the 5 age-related disease categories and shared GO terms include canonical aging pathways identified in model organisms, such as nutrient-sensing signaling, translation, proteostasis, stress responses, and genome maintenance. Taking advantage of the vast amount of genetic data from the GWAS, our findings provide the first direct evidence that conserved pathways of aging simultaneously influence multiple age-related diseases in humans as has been demonstrated in model organisms. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  13. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    Science.gov (United States)

    Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.

    2015-06-01

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  14. Modelling the evolution of common cuckoo host-races: speciation or genetic swamping?

    Science.gov (United States)

    Krüger, O; Kolss, M

    2013-11-01

    Co-evolutionary arms races have provided clear evidence for evolutionary change, especially in host-parasite systems. The evolution of host-specific races in the common cuckoo (Cuculus canorus), however, is also an example where sexual conflict influences the outcome. Cuckoo females benefit from better adaptation to overcome host defences, whereas cuckoo males face a trade-off between the benefits of better adaptation to a host and the benefits of multiple mating with females from other host-races. The outcome of this trade-off might be genetic differentiation or prevention of it by genetic swamping. We use a simulation model to test which outcome is more likely with three sympatric cuckoo host-races. We assume a cost for cuckoo chicks that express a host adaptation allele not suited to their foster host species and that cuckoo males that switch to another host-race experience either a fitness benefit or cost. Over most of the parameter space, cuckoo male host-race fidelity increases significantly with time, and gene flow between host-races ceases within a few thousand to a hundred thousand generations. Our results hence support the idea that common cuckoo host-races might be in the incipient stages of speciation.

  15. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    KAUST Repository

    Hoehndorf, Robert

    2015-06-08

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  16. Genetic assessment of common bean (Phaseolus vulgaris L.) accessions by peroxidase gene-based markers.

    Science.gov (United States)

    Nemli, Seda; Kaya, Hilal Betul; Tanyolac, Bahattin

    2014-06-01

    Peroxidase, a plant-specific oxidoreductase, is a heme-containing glycoprotein encoded by a large multigenic family in plants. Plant peroxidases (POXs, EC 1.11.1.7) play important roles in many self-defense interactions in plants. Here, 67 common bean (Phaseolus vulgaris L.) genotypes were studied using a POX gene-based marker method. Comparison of POX genes could resolve evolutionary relationships in common bean. Eighty fragments were obtained with 20 primer pairs that amplified one (POX8c) to eight (ATP29) bands, with a mean of four bands per primer pair. The average (polymorphic information content) PIC value for the POX products was 0.40. The maximum variation (93%) was found between Turkey (#33) and India (#52) and between Antalya (#33) and India (#53). The minimum variation (0%) was found among four pairs: Bozdag (#2) and Karadeniz (#38), Kirklareli (#11) and Turkey (#15, 16, 43), Bandirma (#13) and Turkey (#15, 16, 43), and Kirklareli (#10) and Bandirma (#22). UPGMA was used to discriminate the common bean genotypes into five clusters, while STRUCTURE software was used to investigate the genetic population structure. The results showed that POX gene family markers can be used to study genotypic diversity and provide new information for breeding programs and common bean improvement practices. © 2013 Society of Chemical Industry.

  17. Common and distinct genetic properties of ESCRT-II components in Drosophila.

    Directory of Open Access Journals (Sweden)

    Hans-Martin Herz

    Full Text Available BACKGROUND: Genetic studies in yeast have identified class E vps genes that form the ESCRT complexes required for protein sorting at the early endosome. In Drosophila, mutations of the ESCRT-II component vps25 cause endosomal defects leading to accumulation of Notch protein and increased Notch pathway activity. These endosomal and signaling defects are thought to account for several phenotypes. Depending on the developmental context, two different types of overgrowth can be detected. Tissue predominantly mutant for vps25 displays neoplastic tumor characteristics. In contrast, vps25 mutant clones in a wild-type background trigger hyperplastic overgrowth in a non-autonomous manner. In addition, vps25 mutant clones also promote apoptotic resistance in a non-autonomous manner. PRINCIPAL FINDINGS: Here, we genetically characterize the remaining ESCRT-II components vps22 and vps36. Like vps25, mutants of vps22 and vps36 display endosomal defects, accumulate Notch protein and--when the tissue is predominantly mutant--show neoplastic tumor characteristics. However, despite these common phenotypes, they have distinct non-autonomous phenotypes. While vps22 mutations cause strong non-autonomous overgrowth, they do not affect apoptotic resistance. In contrast, vps36 mutations increase apoptotic resistance, but have little effect on non-autonomous proliferation. Further characterization reveals that although all ESCRT-II mutants accumulate Notch protein, only vps22 and vps25 mutations trigger Notch activity. CONCLUSIONS/SIGNIFICANCE: The ESCRT-II components vps22, vps25 and vps36 display common and distinct genetic properties. Our data redefine the role of Notch for hyperplastic and neoplastic overgrowth in these mutants. While Notch is required for hyperplastic growth, it appears to be dispensable for neoplastic transformation.

  18. Echinacea for treating the common cold: A randomized controlled trial

    Science.gov (United States)

    Barrett, Bruce; Brown, Roger; Rakel, Dave; Mundt, Marlon; Bone, Kerry; Barlow, Shari; Ewers, Tola

    2011-01-01

    Background Echinacea is widely used to treat common cold. Objective To assess potential benefits of echinacea as common cold treatment. Design Randomized controlled trial with four parallel groups: 1) no pills, 2) placebo pills (blinded), 3) echinacea pills (blinded), or 4) echinacea pills (open-label). (NCT00065715) Setting Community-based trial. Participants People aged 12 to 80 years with new onset common cold. Interventions Extracts of Echinacea purpurea and E. angustifolia root were used to make tablets standardized to alkamide content. Indistinguishable placebo tablets contained only inert ingredients. Measurements The primary outcome was area-under-the-curve global severity, with severity assessed twice daily by self report on the Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Secondary outcomes included interleukin-8 and neutrophil count from nasal wash assessed at intake and two days later. Results Of 719 enrolled, 713 completed the protocol. Participants were 64% female and 88% white, with mean age 33.7 years. Mean global severity was 236 and 258 for blinded and unblinded echinacea, 264 for blinded placebo, and 286 for those without pills. Contrasting the two blinded groups yields a 28 point (95% CI = −69 to 13) trend toward benefit for echinacea (p=0.089). Mean illness duration for the blinded and unblinded echinacea groups was 6.34 and 6.76 days, respectively, compared to 6.87 days for blinded placebo and 7.03 for no pills. Contrasting blinded groups yields a 0.53 day (95% CI = −1.25 to 0.19) trend toward benefit (p = 0.075). Median change interleukin-8 (pg/mL) and neutrophil cell count were: no pills (30, 1), blinded placebo (39, 1), blinded echinacea (58, 2), and open-label echinacea (70, 1), also not statistically significant. Limitations Higher-than-expected variability limited power to detect small-but-potentially-important benefits. Conclusions The observed shorter illness duration and lower severity seen in the echinacea groups were

  19. OVERVIEWS OF THE TREATMENT AND CONTROL OF COMMON FISH DISEASES

    Directory of Open Access Journals (Sweden)

    Madhuri Sharma

    2012-07-01

    Full Text Available Similar to other animals, fish can also suffer from different diseases. All fish carry pathogens and parasites. Disease is a prime agent affecting fish mortality, especially when fish are young. Pathogens which can cause fish diseases comprise: viral infections, bacterial infections, fungal infections, protozoan infections, water mould infection, etc. Fish are also exposed from different environmental pollutants, including drugs and chemicals. The most common fish diseases, particularly in freshwater aquaria, include columnaris, gill disease, ick (ich, dropsy, tail and fin-rot, fungal infections, white spot disease, pop-eye, cloudy eye, swim bladder disease, lice and nematode worms infestation, water quality induced diseases, constipation, anorexia, chilodonella, ergasilus, tuberculosis, glugea, henneguya, hexamita, hole-in-the-head disease, injuries, leeches in aquaria, lymphocystis, marine velvet, and neon-tetra disease, etc. Antibiotics are frequently used to control fish diseases caused by bacteria, but there is an increasing risk of developing antibiotic resistant strains of bacteria. The non-specific immune functions such as bacteriolytic activity and leukocyte function of fish have been improved by some herbs. Plants have been used as traditional medicine since time immemorial to control bacterial, viral, fungal and other diseases.

  20. ATLAS magnet common cryogenic, vacuum, electrical and control systems

    CERN Document Server

    Miele, P; Delruelle, N; Geich-Gimbel, C; Haug, F; Olesen, G; Pengo, R; Sbrissa, E; Tyrvainen, H; ten Kate, H H J

    2004-01-01

    The superconducting Magnet System for the ATLAS detector at the LHC at CERN comprises a Barrel Toroid, two End Cap Toroids and a Central Solenoid with overall dimensions of 20 m diameter by 26 m length and a stored energy of 1.6 GJ. Common proximity cryogenic and electrical systems for the toroids are implemented. The Cryogenic System provides the cooling power for the 3 toroid magnets considered as a single cold mass (600 tons) and for the CS. The 21 kA toroid and the 8 kA solenoid electrical circuits comprise both a switch-mode power supply, two circuit breakers, water cooled bus bars, He cooled current leads and the diode resistor ramp-down unit. The Vacuum System consists of a group of primary rotary pumps and sets of high vacuum diffusion pumps connected to each individual cryostat. The Magnet Safety System guarantees the magnet protection and human safety through slow and fast dump treatment. The Magnet Control System ensures control, regulation and monitoring of the operation of the magnets. The update...

  1. Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake

    NARCIS (Netherlands)

    T. Tanaka (Toshiko); J.S. Ngwa; F.J.A. van Rooij (Frank); M.C. Zillikens (Carola); M.K. Wojczynski (Mary ); A.C. Frazier-Wood (Alexis); D.K. Houston (Denise); S. Kanoni (Stavroula); R.N. Lemaitre (Rozenn ); J. Luan; V. Mikkilä (Vera); F. Renström (Frida); E. Sonestedt (Emily); J.H. Zhao (Jing); A.Y. Chu (Audrey); L. Qi (Lu); D.I. Chasman (Daniel); M.C. De Oliveira Otto (Marcia); E.J. Dhurandhar (Emily); M.F. Feitosa (Mary Furlan); I. Johansson (Ingegerd); K-T. Khaw (Kay-Tee); K. Lohman (Kurt); A. Manichaikul (Ani); N.M. McKeown (Nicola ); D. Mozaffarian (Dariush); A.B. Singleton (Andrew); K. Stirrups (Kathy); J. Viikari (Jorma); Z. Ye (Zheng); S. Bandinelli (Stefania); I. Barroso (Inês); P. Deloukas (Panagiotis); N.G. Forouhi (Nita); A. Hofman (Albert); Y. Liu (Yongmei); L.-P. Lyytikäinen (Leo-Pekka); K.E. North (Kari); M. Dimitriou (Maria); G. Hallmans (Göran); M. Kähönen (Mika); C. Langenberg (Claudia); J.M. Ordovas (Jose); A.G. Uitterlinden (André); F.B. Hu (Frank); I.-P. Kalafati (Ioanna-Panagiota); O. Raitakari (Olli); O.H. Franco (Oscar); A. Johnson (Anthony); V. Emilsson (Valur); J.A. Schrack (Jennifer); R.D. Semba; D.S. Siscovick (David); D.K. Arnett (Donna); I.B. Borecki (Ingrid); P.W. Franks (Paul); S.B. Kritchevsky (Stephen); R.J.F. Loos (Ruth); M. Orho-Melander (Marju); J.I. Rotter (Jerome); N.J. Wareham (Nick); J.C.M. Witteman (Jacqueline); L. Ferrucci (Luigi); G.V. Dedoussis (George); L.A. Cupples (Adrienne); J.A. Nettleton (Jennifer )

    2013-01-01

    textabstractBackground: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. Objective: The objective of the study was to identify common genetic variants that are associated with macronutrient intake. D

  2. Mammographic Breast Density and Common Genetic Variants in Breast Cancer Risk Prediction.

    Directory of Open Access Journals (Sweden)

    Charmaine Pei Ling Lee

    Full Text Available Known prediction models for breast cancer can potentially by improved by the addition of mammographic density and common genetic variants identified in genome-wide associations studies known to be associated with risk of the disease. We evaluated the benefit of including mammographic density and the cumulative effect of genetic variants in breast cancer risk prediction among women in a Singapore population.We estimated the risk of breast cancer using a prospective cohort of 24,161 women aged 50 to 64 from Singapore with available mammograms and known risk factors for breast cancer who were recruited between 1994 and 1997. We measured mammographic density using the medio-lateral oblique views of both breasts. Each woman's genotype for 75 SNPs was simulated based on the genotype frequency obtained from the Breast Cancer Association Consortium data and the cumulative effect was summarized by a genetic risk score (GRS. Any improvement in the performance of our proposed prediction model versus one containing only variables from the Gail model was assessed by changes in receiver-operating characteristic and predictive values.During 17 years of follow-up, 680 breast cancer cases were diagnosed. The multivariate-adjusted hazard ratios (95% confidence intervals were 1.60 (1.22-2.10, 2.20 (1.65-2.92, 2.33 (1.71-3.20, 2.12 (1.43-3.14, and 3.27 (2.24-4.76 for the corresponding mammographic density categories: 11-20cm2, 21-30cm2, 31-40cm2, 41-50cm2, 51-60cm2, and 1.10 (1.03-1.16 for GRS. At the predicted absolute 10-year risk thresholds of 2.5% and 3.0%, a model with mammographic density and GRS could correctly identify 0.9% and 0.5% more women who would develop the disease compared to a model using only the Gail variables, respectively.Mammographic density and common genetic variants can improve the discriminatory power of an established breast cancer risk prediction model among females in Singapore.

  3. Disentangling genetic vs. environmental causes of sex determination in the common frog, Rana temporaria.

    Science.gov (United States)

    Matsuba, Chikako; Miura, Ikuo; Merilä, Juha

    2008-01-08

    Understanding of sex ratio dynamics in a given species requires understanding its sex determination system, as well as access for reliable tools for sex identification at different life stages. As in the case of many other amphibians, the common frogs (Rana temporaria) do not have well differentiated sex chromosomes, and an identification of individuals' genetic sex may be complicated by sex reversals. Here, we report results of studies shedding light on the sex determination system and sex ratio variation in this species. A microsatellite locus RtSB03 was found to be sex-linked in four geographically disparate populations, suggesting male heterogamy in common frogs. However, in three other populations examined, no or little evidence for sex-linkage was detected suggesting either ongoing/recent recombination events, and/or frequent sex-reversals. Comparison of inheritance patterns of alleles in RtSB03 and phenotypic sex within sibships revealed a mixed evidence for sex-linkage: all individuals with male phenotype carried a male specific allele in one population, whereas results were more mixed in another population. These results make sense only if we assume that the RtSB03 locus is linked to male sex determination factor in some, but not in all common frog populations, and if phenotypic sex-reversals - for which there is earlier evidence from this species - are frequently occurring.

  4. Disentangling genetic vs. environmental causes of sex determination in the common frog, Rana temporaria

    Directory of Open Access Journals (Sweden)

    Merilä Juha

    2008-01-01

    Full Text Available Abstract Background Understanding of sex ratio dynamics in a given species requires understanding its sex determination system, as well as access for reliable tools for sex identification at different life stages. As in the case of many other amphibians, the common frogs (Rana temporaria do not have well differentiated sex chromosomes, and an identification of individuals' genetic sex may be complicated by sex reversals. Here, we report results of studies shedding light on the sex determination system and sex ratio variation in this species. Results A microsatellite locus RtSB03 was found to be sex-linked in four geographically disparate populations, suggesting male heterogamy in common frogs. However, in three other populations examined, no or little evidence for sex-linkage was detected suggesting either ongoing/recent recombination events, and/or frequent sex-reversals. Comparison of inheritance patterns of alleles in RtSB03 and phenotypic sex within sibships revealed a mixed evidence for sex-linkage: all individuals with male phenotype carried a male specific allele in one population, whereas results were more mixed in another population. Conclusion These results make sense only if we assume that the RtSB03 locus is linked to male sex determination factor in some, but not in all common frog populations, and if phenotypic sex-reversals – for which there is earlier evidence from this species – are frequently occurring.

  5. Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer.

    Science.gov (United States)

    Garcia-Closas, Montserrat; Rothman, Nathaniel; Figueroa, Jonine D; Prokunina-Olsson, Ludmila; Han, Summer S; Baris, Dalsu; Jacobs, Eric J; Malats, Nuria; De Vivo, Immaculata; Albanes, Demetrius; Purdue, Mark P; Sharma, Sapna; Fu, Yi-Ping; Kogevinas, Manolis; Wang, Zhaoming; Tang, Wei; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Johnson, Alison; Schwenn, Molly; Karagas, Margaret R; Schned, Alan; Andriole, Gerald; Grubb, Robert; Black, Amanda; Gapstur, Susan M; Thun, Michael; Diver, William Ryan; Weinstein, Stephanie J; Virtamo, Jarmo; Hunter, David J; Caporaso, Neil; Landi, Maria Teresa; Hutchinson, Amy; Burdett, Laurie; Jacobs, Kevin B; Yeager, Meredith; Fraumeni, Joseph F; Chanock, Stephen J; Silverman, Debra T; Chatterjee, Nilanjan

    2013-04-01

    Bladder cancer results from the combined effects of environmental and genetic factors, smoking being the strongest risk factor. Evaluating absolute risks resulting from the joint effects of smoking and genetic factors is critical to assess the public health relevance of genetic information. Analyses included up to 3,942 cases and 5,680 controls of European background in seven studies. We tested for multiplicative and additive interactions between smoking and 12 susceptibility loci, individually and combined as a polygenic risk score (PRS). Thirty-year absolute risks and risk differences by levels of the PRS were estimated for U.S. males aged 50 years. Six of 12 variants showed significant additive gene-environment interactions, most notably NAT2 (P = 7 × 10(-4)) and UGT1A6 (P = 8 × 10(-4)). The 30-year absolute risk of bladder cancer in U.S. males was 6.2% for all current smokers. This risk ranged from 2.9% for current smokers in the lowest quartile of the PRS to 9.9% for current smokers in the upper quartile. Risk difference estimates indicated that 8,200 cases would be prevented if elimination of smoking occurred in 100,000 men in the upper PRS quartile compared with 2,000 cases prevented by a similar effort in the lowest PRS quartile (P(additive) = 1 × 10(-4)). Thus, the potential impact of eliminating smoking on the number of bladder cancer cases prevented is larger for individuals at higher than lower genetic risk. Our findings could have implications for targeted prevention strategies. However, other smoking-related diseases, as well as practical and ethical considerations, need to be considered before any recommendations could be made. ©2012 AACR.

  6. DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases

    Science.gov (United States)

    Bettencourt, Conceição; Hensman‐Moss, Davina; Flower, Michael; Wiethoff, Sarah; Brice, Alexis; Goizet, Cyril; Stevanin, Giovanni; Koutsis, Georgios; Karadima, Georgia; Panas, Marios; Yescas‐Gómez, Petra; García‐Velázquez, Lizbeth Esmeralda; Alonso‐Vilatela, María Elisa; Lima, Manuela; Raposo, Mafalda; Traynor, Bryan; Sweeney, Mary; Wood, Nicholas; Giunti, Paola; Durr, Alexandra; Holmans, Peter; Houlden, Henry; Tabrizi, Sarah J.

    2016-01-01

    Objective The polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome‐wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases. Methods We assembled an independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and genotyped single‐nucleotide polymorphisms (SNPs) selected from the most significant hits in the HD study. Results In the analysis of DNA repair genes as a group, we found the most significant association with age at onset when grouping all polyglutamine diseases (HD+SCAs; p = 1.43 × 10–5). In individual SNP analysis, we found significant associations for rs3512 in FAN1 with HD+SCAs (p = 1.52 × 10–5) and all SCAs (p = 2.22 × 10–4) and rs1805323 in PMS2 with HD+SCAs (p = 3.14 × 10–5), all in the same direction as in the HD GWAS. Interpretation We show that DNA repair genes significantly modify age at onset in HD and SCAs, suggesting a common pathogenic mechanism, which could operate through the observed somatic expansion of repeats that can be modulated by genetic manipulation of DNA repair in disease models. This offers novel therapeutic opportunities in multiple diseases. Ann Neurol 2016;79:983–990 PMID:27044000

  7. Genome sequence and genetic diversity of the common carp, Cyprinus carpio.

    Science.gov (United States)

    Xu, Peng; Zhang, Xiaofeng; Wang, Xumin; Li, Jiongtang; Liu, Guiming; Kuang, Youyi; Xu, Jian; Zheng, Xianhu; Ren, Lufeng; Wang, Guoliang; Zhang, Yan; Huo, Linhe; Zhao, Zixia; Cao, Dingchen; Lu, Cuiyun; Li, Chao; Zhou, Yi; Liu, Zhanjiang; Fan, Zhonghua; Shan, Guangle; Li, Xingang; Wu, Shuangxiu; Song, Lipu; Hou, Guangyuan; Jiang, Yanliang; Jeney, Zsigmond; Yu, Dan; Wang, Li; Shao, Changjun; Song, Lai; Sun, Jing; Ji, Peifeng; Wang, Jian; Li, Qiang; Xu, Liming; Sun, Fanyue; Feng, Jianxin; Wang, Chenghui; Wang, Shaolin; Wang, Baosen; Li, Yan; Zhu, Yaping; Xue, Wei; Zhao, Lan; Wang, Jintu; Gu, Ying; Lv, Weihua; Wu, Kejing; Xiao, Jingfa; Wu, Jiayan; Zhang, Zhang; Yu, Jun; Sun, Xiaowen

    2014-11-01

    The common carp, Cyprinus carpio, is one of the most important cyprinid species and globally accounts for 10% of freshwater aquaculture production. Here we present a draft genome of domesticated C. carpio (strain Songpu), whose current assembly contains 52,610 protein-coding genes and approximately 92.3% coverage of its paleotetraploidized genome (2n = 100). The latest round of whole-genome duplication has been estimated to have occurred approximately 8.2 million years ago. Genome resequencing of 33 representative individuals from worldwide populations demonstrates a single origin for C. carpio in 2 subspecies (C. carpio Haematopterus and C. carpio carpio). Integrative genomic and transcriptomic analyses were used to identify loci potentially associated with traits including scaling patterns and skin color. In combination with the high-resolution genetic map, the draft genome paves the way for better molecular studies and improved genome-assisted breeding of C. carpio and other closely related species.

  8. Genetic control of human brain transcript expression in Alzheimer disease.

    Science.gov (United States)

    Webster, Jennifer A; Gibbs, J Raphael; Clarke, Jennifer; Ray, Monika; Zhang, Weixiong; Holmans, Peter; Rohrer, Kristen; Zhao, Alice; Marlowe, Lauren; Kaleem, Mona; McCorquodale, Donald S; Cuello, Cindy; Leung, Doris; Bryden, Leslie; Nath, Priti; Zismann, Victoria L; Joshipura, Keta; Huentelman, Matthew J; Hu-Lince, Diane; Coon, Keith D; Craig, David W; Pearson, John V; Heward, Christopher B; Reiman, Eric M; Stephan, Dietrich; Hardy, John; Myers, Amanda J

    2009-04-01

    We recently surveyed the relationship between the human brain transcriptome and genome in a series of neuropathologically normal postmortem samples. We have now analyzed additional samples with a confirmed pathologic diagnosis of late-onset Alzheimer disease (LOAD; final n = 188 controls, 176 cases). Nine percent of the cortical transcripts that we analyzed had expression profiles correlated with their genotypes in the combined cohort, and approximately 5% of transcripts had SNP-transcript relationships that could distinguish LOAD samples. Two of these transcripts have been previously implicated in LOAD candidate-gene SNP-expression screens. This study shows how the relationship between common inherited genetic variants and brain transcript expression can be used in the study of human brain disorders. We suggest that studying the transcriptome as a quantitative endo-phenotype has greater power for discovering risk SNPs influencing expression than the use of discrete diagnostic categories such as presence or absence of disease.

  9. Web-based, participant-driven studies yield novel genetic associations for common traits.

    Directory of Open Access Journals (Sweden)

    Nicholas Eriksson

    2010-06-01

    Full Text Available Despite the recent rapid growth in genome-wide data, much of human variation remains entirely unexplained. A significant challenge in the pursuit of the genetic basis for variation in common human traits is the efficient, coordinated collection of genotype and phenotype data. We have developed a novel research framework that facilitates the parallel study of a wide assortment of traits within a single cohort. The approach takes advantage of the interactivity of the Web both to gather data and to present genetic information to research participants, while taking care to correct for the population structure inherent to this study design. Here we report initial results from a participant-driven study of 22 traits. Replications of associations (in the genes OCA2, HERC2, SLC45A2, SLC24A4, IRF4, TYR, TYRP1, ASIP, and MC1R for hair color, eye color, and freckling validate the Web-based, self-reporting paradigm. The identification of novel associations for hair morphology (rs17646946, near TCHH; rs7349332, near WNT10A; and rs1556547, near OFCC1, freckling (rs2153271, in BNC2, the ability to smell the methanethiol produced after eating asparagus (rs4481887, near OR2M7, and photic sneeze reflex (rs10427255, near ZEB2, and rs11856995, near NR2F2 illustrates the power of the approach.

  10. Web-based, participant-driven studies yield novel genetic associations for common traits.

    Science.gov (United States)

    Eriksson, Nicholas; Macpherson, J Michael; Tung, Joyce Y; Hon, Lawrence S; Naughton, Brian; Saxonov, Serge; Avey, Linda; Wojcicki, Anne; Pe'er, Itsik; Mountain, Joanna

    2010-06-24

    Despite the recent rapid growth in genome-wide data, much of human variation remains entirely unexplained. A significant challenge in the pursuit of the genetic basis for variation in common human traits is the efficient, coordinated collection of genotype and phenotype data. We have developed a novel research framework that facilitates the parallel study of a wide assortment of traits within a single cohort. The approach takes advantage of the interactivity of the Web both to gather data and to present genetic information to research participants, while taking care to correct for the population structure inherent to this study design. Here we report initial results from a participant-driven study of 22 traits. Replications of associations (in the genes OCA2, HERC2, SLC45A2, SLC24A4, IRF4, TYR, TYRP1, ASIP, and MC1R) for hair color, eye color, and freckling validate the Web-based, self-reporting paradigm. The identification of novel associations for hair morphology (rs17646946, near TCHH; rs7349332, near WNT10A; and rs1556547, near OFCC1), freckling (rs2153271, in BNC2), the ability to smell the methanethiol produced after eating asparagus (rs4481887, near OR2M7), and photic sneeze reflex (rs10427255, near ZEB2, and rs11856995, near NR2F2) illustrates the power of the approach.

  11. Genetic Diversity and Symbiotic Efficiency of Indigenous Common Bean Rhizobia in Croatia.

    Science.gov (United States)

    Pohajda, Ines; Babić, Katarina Huić; Rajnović, Ivana; Kajić, Sanja; Sikora, Sanja

    2016-12-01

    Nodule bacteria (rhizobia) in symbiotic associations with legumes enable considerable entries of biologically fixed nitrogen into soil. Efforts are therefore made to intensify the natural process of symbiotic nitrogen fixation by legume inoculation. Studies of field populations of rhizobia open up the possibility to preserve and probably exploit some indigenous strains with hidden symbiotic or ecological potentials. The main aim of the present study is to determine genetic diversity of common bean rhizobia isolated from different field sites in central Croatia and to evaluate their symbiotic efficiency and compatibility with host plants. The isolation procedure revealed that most soil samples contained no indigenous common bean rhizobia. The results indicate that the cropping history had a significant impact on the presence of indigenous strains. Although all isolates were found to belong to species Rhizobium leguminosarum, significant genetic diversity at the strain level was determined. Application of both random amplification of polymorphic DNA (RAPD) and enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC- -PCR) methods resulted in similar grouping of strains. Symbiotic efficiency of indigenous rhizobia as well as their compatibility with two commonly grown bean varieties were tested in field experiments. Application of indigenous rhizobial strains as inoculants resulted in significantly different values of nodulation, seed yield as well as plant nitrogen and seed protein contents. The most abundant nodulation and the highest plant nitrogen and protein contents were determined in plants inoculated with R. leguminosarum strains S17/2 and S21/6. Although, in general, the inoculation had a positive impact on seed yield, differences depending on the applied strain were not determined. The overall results show the high degree of symbiotic efficiency of the specific indigenous strain S21/6. These results indicate different symbiotic

  12. Genetic Diversity and Symbiotic Efficiency of Indigenous Common Bean Rhizobia in Croatia

    Directory of Open Access Journals (Sweden)

    Ines Pohajda

    2016-01-01

    Full Text Available Nodule bacteria (rhizobia in symbiotic associations with legumes enable considerable entries of biologically fixed nitrogen into soil. Efforts are therefore made to intensify the natural process of symbiotic nitrogen fixation by legume inoculation. Studies of field populationsof rhizobia open up the possibility to preserve and probably exploit some indigenous strains with hidden symbiotic or ecological potentials. The main aim of the present study is to determine genetic diversity of common bean rhizobia isolated from different field sites in central Croatia and to evaluate their symbiotic efficiency and compatibility with host plants. The isolation procedure revealed that most soil samples contained no indigenous common bean rhizobia. The results indicate that the cropping history had a significant impact on the presence of indigenous strains. Although all isolates were found to belong to species Rhizobium leguminosarum, significant genetic diversity at the strain level was determined. Application of both random amplifi cation of polymorphic DNA (RAPD and enterobacterial repetitive intergenic consensus–polymerase chain reaction (ERIC-PCR methods resulted in similar grouping of strains. Symbiotic efficiency of indigenous rhizobia as well as their compatibility with two commonly grown bean varieties were tested in field experiments. Application of indigenous rhizobial strains as inoculants resulted in significantly different values of nodulation, seed yield as well as plant nitrogen and seed protein contents. The most abundant nodulation and the highest plant nitrogen and protein contents were determined in plants inoculated with R. leguminosarum strains S17/2 and S21/6. Although, in general, the inoculation had a positive impact on seed yield, differences depending on the applied strain were not determined. The overall results show the high degree of symbiotic efficiency of the specific indigenous strain S21/6. These results indicate different

  13. A Common Genetic Variant Risk Score is Associated with Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study.

    Science.gov (United States)

    Strauss, David G; Vicente, Jose; Johannesen, Lars; Blinova, Ksenia; Mason, Jay W; Weeke, Peter; Behr, Elijah R; Roden, Dan M; Woosley, Raymond; Kosova, Gulum; Rosenberg, Michael A; Newton-Cheh, Christopher

    2017-02-17

    Background -Drug-induced QT interval prolongation, a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications. The contribution of common genetic variants previously associated with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known. Methods -We tested the hypothesis that a weighted combination of common genetic variants contributing to QT interval at baseline, identified through genome-wide association studies, can predict individual response to multiple QT-prolonging drugs. Genetic analysis of 22 subjects was performed in a secondary analysis of a randomized, double-blind, placebo-controlled, cross-over trial of 3 QT-prolonging drugs with 15 time-matched QT and plasma drug concentration measurements. Subjects received single doses of dofetilide, quinidine, ranolazine and placebo. The outcome was the correlation between a genetic QT score comprising 61 common genetic variants and the slope of an individual subject's drug-induced increase in heart rate corrected QT (QTc) vs. drug concentration. Results -The genetic QT score was correlated with drug-induced QTc prolongation. Among white subjects, genetic QT score explained 30% of the variability in response to dofetilide (r = 0.55 [95% CI, 0.09-0.81], P = 0.02), 23% in response to quinidine (r = 0.48 [95% CI, -0.03 to 0.79], P = 0.06) and 27% in response to ranolazine (r = 0.52 [95% CI, 0.05 to 0.80], P = 0.03). Furthermore, the genetic QT score was a significant predictor of drug-induced torsade de pointes in an independent sample of 216 cases compared to 771 controls (r(2) = 12%, P = 1x10(-7)). Conclusions -We demonstrate that a genetic QT score comprising 61 common genetic variants explains a significant proportion of the variability in drug-induced QT prolongation and is a significant predictor of drug-induced torsade de pointes. These findings highlight an opportunity for recent genetic discoveries to improve

  14. Genetic noise control via protein oligomerization

    Directory of Open Access Journals (Sweden)

    Almaas Eivind

    2008-11-01

    Full Text Available Abstract Background Gene expression in a cell entails random reaction events occurring over disparate time scales. Thus, molecular noise that often results in phenotypic and population-dynamic consequences sets a fundamental limit to biochemical signaling. While there have been numerous studies correlating the architecture of cellular reaction networks with noise tolerance, only a limited effort has been made to understand the dynamic role of protein-protein interactions. Results We have developed a fully stochastic model for the positive feedback control of a single gene, as well as a pair of genes (toggle switch, integrating quantitative results from previous in vivo and in vitro studies. In particular, we explicitly account for the fast binding-unbinding kinetics among proteins, RNA polymerases, and the promoter/operator sequences of DNA. We find that the overall noise-level is reduced and the frequency content of the noise is dramatically shifted to the physiologically irrelevant high-frequency regime in the presence of protein dimerization. This is independent of the choice of monomer or dimer as transcription factor and persists throughout the multiple model topologies considered. For the toggle switch, we additionally find that the presence of a protein dimer, either homodimer or heterodimer, may significantly reduce its random switching rate. Hence, the dimer promotes the robust function of bistable switches by preventing the uninduced (induced state from randomly being induced (uninduced. Conclusion The specific binding between regulatory proteins provides a buffer that may prevent the propagation of fluctuations in genetic activity. The capacity of the buffer is a non-monotonic function of association-dissociation rates. Since the protein oligomerization per se does not require extra protein components to be expressed, it provides a basis for the rapid control of intrinsic or extrinsic noise. The stabilization of regulatory circuits

  15. Associations of two common genetic variants with breast cancer risk in a chinese population: a stratified interaction analysis.

    Directory of Open Access Journals (Sweden)

    Yuxiang Lin

    Full Text Available Recent genome-wide association studies (GWAS have identified a series of new genetic susceptibility loci for breast cancer (BC. However, the correlations between these variants and breast cancer are still not clear. In order to explore the role of breast cancer susceptibility variants in a Southeast Chinese population, we genotyped two common SNPs at chromosome 6q25 (rs2046210 and in TOX3 (rs4784227 in a case-control study with a total of 702 breast cancer cases and 794 healthy-controls. In addition, we also evaluated the multiple interactions among genetic variants, risk factors, and tumor subtypes. Associations of genotypes with breast cancer risk was evaluated using multivariate logistic regression to estimate odds ratios (OR and their 95% confidence intervals (95% CI. The results indicated that both polymorphisms were significantly associated with the risk of breast cancer, with per allele OR = 1.35, (95%CI = 1.17-1.57 for rs2046210 and per allele OR = 1.24 (95%CI = 1.06-1.45 for rs4784227. Furthermore, in subgroup stratified analyses, we observed that the T allele of rs4784227 was significantly associated with elevated OR among postmenopausal populations (OR = 1.44, 95%CI 1.11-1.87 but not in premenopausal populations, with the heterogeneity P value of P = 0.064. These findings suggest that the genetic variants at chromosome 6q25 and in the TOX3 gene may play important roles in breast cancer development in a Chinese population and the underlying biological mechanisms need to be further elucidated.

  16. Genetic diversity of indigenous common bean (Phaseolus vulgaris L. rhizobia from the state of Minas Gerais, Brazil

    Directory of Open Access Journals (Sweden)

    Adalgisa Ribeiro Torres

    2009-12-01

    Full Text Available We characterized indigenous common bean rhizobia from five districts of the state of Minas Gerais, Brazil. The isolates were trapped by two common bean varieties, the Mineiro Precoce (Andean origin and Ouro Negro (Mesoamerican origin. Analysis by BOX-PCR of selected isolates detected a high level of genetic diversity.

  17. Genetic diversity of indigenous common bean (Phaseolus vulgaris L.) rhizobia from the state of Minas Gerais, Brazil

    Science.gov (United States)

    Torres, Adalgisa Ribeiro; Cursino, Luciana; Muro-Abad, Júpiter Israel; Gomes, Eliane Aparecida; de Araújo, Elza Fernandes; Hungria, Mariangela; Cassini, Sérvio Túlio Alves

    2009-01-01

    We characterized indigenous common bean rhizobia from five districts of the state of Minas Gerais, Brazil. The isolates were trapped by two common bean varieties, the Mineiro Precoce (Andean origin) and Ouro Negro (Mesoamerican origin). Analysis by BOX-PCR of selected isolates detected a high level of genetic diversity. PMID:24031433

  18. Genetic Algorithm Based Proportional Integral Controller Design for Induction Motor

    Directory of Open Access Journals (Sweden)

    Mohanasundaram Kuppusamy

    2011-01-01

    Full Text Available Problem statement: This study has expounded the application of evolutionary computation method namely Genetic Algorithm (GA for estimation of feedback controller parameters for induction motor. GA offers certain advantages such as simple computational steps, derivative free optimization, reduced number of iterations and assured near global optima. The development of the method is well documented and computed and measured results are presented. Approach: The design of PI controller parameter for three phase induction motor drives was done using Genetic Algorithm. The objective function of motor current reduction, using PI controller, at starting is formulated as an optimization problem and solved with Genetic Algorithm. Results: The results showed the selected values of PI controller parameter using genetic algorithm approach, with objective of induction motor starting current reduction. Conclusions/Recommendation: The results proved the robustness and easy implementation of genetic algorithm selection of PI parameters for induction motor starting.

  19. Common genetic variation in the human CTF1 locus, encoding cardiotrophin-1, determines insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Stefan Z Lutz

    Full Text Available AIMS/HYPOTHESIS: Recently, cardiotrophin-1, a member of the interleukin-6 family of cytokines was described to protect beta-cells from apoptosis, to improve glucose-stimulated insulin secretion and insulin resistance, and to prevent streptozotocin-induced diabetes in mice. Here, we studied whether common single nucleotide polymorphisms (SNPs in the CTF1 locus, encoding cardiotrophin-1, influence insulin secretion and insulin sensitivity in humans. METHODS: We genotyped 1,771 German subjects for three CTF1 tagging SNPs (rs1046276, rs1458201, and rs8046707. The subjects were metabolically characterized by an oral glucose tolerance test. Subgroups underwent magnetic resonance (MR imaging/spectroscopy and hyperinsulinaemic-euglycaemic clamps. RESULTS: After appropriate adjustment, the minor allele of CTF1 SNP rs8046707 was significantly associated with decreased in vivo measures of insulin sensitivity. The other tested SNPs were not associated with OGTT-derived sensitivity parameters, nor did the three tested SNPs show any association with OGTT-derived parameters of insulin release. In the MR subgroup, SNP rs8046707 was nominally associated with lower visceral adipose tissue. Furthermore, the SNP rs1458201 showed a nominal association with increased VLDL levels. CONCLUSIONS: In conclusion, this study, even though preliminary and awaiting further confirmation by independent replication, provides first evidence that common genetic variation in CTF1 could contribute to insulin sensitivity in humans. Our SNP data indicate an insulin-desensitizing effect of cardiotrophin-1 and underline that cardiotrophin-1 represents an interesting target to influence insulin sensitivity.

  20. Rhizobial exopolysaccharides: genetic control and symbiotic functions

    Directory of Open Access Journals (Sweden)

    Mazur Andrzej

    2006-02-01

    Full Text Available Abstract Specific complex interactions between soil bacteria belonging to Rhizobium, Sinorhizobium, Mesorhizobium, Phylorhizobium, Bradyrhizobium and Azorhizobium commonly known as rhizobia, and their host leguminous plants result in development of root nodules. Nodules are new organs that consist mainly of plant cells infected with bacteroids that provide the host plant with fixed nitrogen. Proper nodule development requires the synthesis and perception of signal molecules such as lipochitooligosaccharides, called Nod factors that are important for induction of nodule development. Bacterial surface polysaccharides are also crucial for establishment of successful symbiosis with legumes. Sugar polymers of rhizobia are composed of a number of different polysaccharides, such as lipopolysaccharides (LPS, capsular polysaccharides (CPS or K-antigens, neutral β-1, 2-glucans and acidic extracellular polysaccharides (EPS. Despite extensive research, the molecular function of the surface polysaccharides in symbiosis remains unclear. This review focuses on exopolysaccharides that are especially important for the invasion that leads to formation of indetermined (with persistent meristem type of nodules on legumes such as clover, vetch, peas or alfalfa. The significance of EPS synthesis in symbiotic interactions of Rhizobium leguminosarum with clover is especially noticed. Accumulating data suggest that exopolysaccharides may be involved in invasion and nodule development, bacterial release from infection threads, bacteroid development, suppression of plant defense response and protection against plant antimicrobial compounds. Rhizobial exopolysaccharides are species-specific heteropolysaccharide polymers composed of common sugars that are substituted with non-carbohydrate residues. Synthesis of repeating units of exopolysaccharide, their modification, polymerization and export to the cell surface is controlled by clusters of genes, named exo/exs, exp or

  1. Population genetics and management units of invasive common carp Cyprinus carpio in the Murray-Darling Basin, Australia.

    Science.gov (United States)

    Haynes, G D; Gilligan, D M; Grewe, P; Nicholas, F W

    2009-08-01

    Common carp Cyprinus carpio were introduced into Australia on several occasions and are now the dominant fish in the Murray-Darling Basin (MDB), the continent's largest river system. In this study, variability at 14 microsatellite loci was examined in C. carpio (n = 1037) from 34 sites throughout the major rivers in the MDB, from 3 cultured populations, from Prospect Reservoir in the Sydney Basin and from Lake Sorrell in Tasmania. Consistent with previous studies, assignment testing indicated that the Boolara, Yanco and koi strains of C. carpio are present in the MDB. Unique to this study, however, the Prospect strain was widely distributed throughout the MDB. Significant genetic structuring of populations (Fisher's exact test, AMOVA and distribution of the different strains) amongst the MDB sub-drainages was detected, and was strongly associated with contemporary barriers to dispersal and population history. The distributions of the strains were used to infer the history of introduction and spread of C. carpio in the MDB. Fifteen management units are proposed for control programmes that have high levels of genetic diversity, contain multiple interbreeding strains and show no evidence of founder effects or recent population bottlenecks.

  2. Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels.

    Directory of Open Access Journals (Sweden)

    Tina Ristau

    Full Text Available Age-related macular degeneration (AMD is a common condition that leads to severe vision loss and dysregulation of the complement system is thought to be associated with the disease. To investigate associations of polymorphisms in AMD susceptibility genes with systemic complement activation, 2655 individuals were genotyped for 32 single nucleotide polymorphisms (SNPs in or near 23 AMD associated risk genes. Component 3 (C3 and its catabolic fragment C3d were measured in serum and AMD staging was performed using multimodal imaging. The C3d/C3 ratio was calculated and associations with environmental factors, SNPs and various haplotypes of complement factor H (CFH genes and complement factor B (CFB genes were analyzed. Linear models were built to measure the influence of genetic variants on the C3d/C3 ratio. The study cohort included 1387 patients with AMD and 1268 controls. Higher C3d/C3 ratios were found for current smoker (p = 0.002, higher age (p = 1.56 × 10(-7, AMD phenotype (p = 1.15 × 10(-11 and the two SNPs in the C3 gene rs6795735 (p = 0.04 and rs2230199 (p = 0.04. Lower C3d/C3 ratios were found for diabetes (p = 2.87 × 10(-6, higher body mass index (p = 1.00 × 10(-13, the SNPs rs1410996 (p = 0.0001, rs800292 (p = 0.003, rs12144939 (p = 4.60 × 10(-6 in CFH, rs4151667 (p = 1.01 × 10(-5 in CFB and individual haplotypes in CFH and CFB. The linear model revealed a corrected R-square of 0.063 including age, smoking status, gender, and genetic polymorphisms explaining 6.3% of the C3d/C3 ratio. After adding the AMD status the corrected R-square was 0.067. In conclusion, none of the evaluated genetic polymorphisms showed an association with increased systemic complement activation apart from two SNPs in the C3 gene. Major genetic and non-genetic factors for AMD were not associated with systemic complement activation.

  3. The Last Universal Common Ancestor: emergence, constitution and genetic legacy of an elusive forerunner

    Directory of Open Access Journals (Sweden)

    Labedan Bernard

    2008-07-01

    Full Text Available Abstract Background Since the reclassification of all life forms in three Domains (Archaea, Bacteria, Eukarya, the identity of their alleged forerunner (Last Universal Common Ancestor or LUCA has been the subject of extensive controversies: progenote or already complex organism, prokaryote or protoeukaryote, thermophile or mesophile, product of a protracted progression from simple replicators to complex cells or born in the cradle of "catalytically closed" entities? We present a critical survey of the topic and suggest a scenario. Results LUCA does not appear to have been a simple, primitive, hyperthermophilic prokaryote but rather a complex community of protoeukaryotes with a RNA genome, adapted to a broad range of moderate temperatures, genetically redundant, morphologically and metabolically diverse. LUCA's genetic redundancy predicts loss of paralogous gene copies in divergent lineages to be a significant source of phylogenetic anomalies, i.e. instances where a protein tree departs from the SSU-rRNA genealogy; consequently, horizontal gene transfer may not have the rampant character assumed by many. Examining membrane lipids suggest LUCA had sn1,2 ester fatty acid lipids from which Archaea emerged from the outset as thermophilic by "thermoreduction," with a new type of membrane, composed of sn2,3 ether isoprenoid lipids; this occurred without major enzymatic reconversion. Bacteria emerged by reductive evolution from LUCA and some lineages further acquired extreme thermophily by convergent evolution. This scenario is compatible with the hypothesis that the RNA to DNA transition resulted from different viral invasions as proposed by Forterre. Beyond the controversy opposing "replication first" to metabolism first", the predictive arguments of theories on "catalytic closure" or "compositional heredity" heavily weigh in favour of LUCA's ancestors having emerged as complex, self-replicating entities from which a genetic code arose under natural

  4. 鲤抗病育种研究进展%Genetic improvement of disease resistance in common carp

    Institute of Scientific and Technical Information of China (English)

    贾智英; 石连玉; 孙效文

    2012-01-01

    尽管鲤养殖业取得了巨大成就,但病害问题仍然是其发展所面临的一个重要制约因素。病害防控方法,主要有环境防控、药物控制和疫苗法,而运用遗传改良来提高鲤抗病力被认为是一种切实可行的方法。虽然以提高生长为目的的多项鲤育种计划已经取得了成功,但有关抗病育种相关研究仍处于起步阶段。利用鲤群体所存在的有益遗传变异,选择合适的育种方法,积极开展抗病选育应该是今后鲤养殖业所必须关注的重要研究内容。从环境胁迫对抗病性状的影响、抗病性状的遗传学基础、抗病性状与其他性状的关系、抗病性状的测定、抗病育种具体方法等方面较系统地介绍了利用遗传改良来提高鲤抗病力的相关研究进展。研究亮点:抗病力是养殖鱼类一个重要经济性状,但由于基础研究薄弱、有效评价方法缺乏等原因,致使抗病选育工作远落后于以生长等性状为目标的育种研究。本文综述了鲤抗病育种相关研究进展,为鲤和其他鱼类的抗病育种工作提供了重要的参考。%Despite impressive progress in common carp farming during the last years, the impact of fish diseases is still an important problem in aquaculture. Current methods to control diseases consist, among others, of euhural environment control, medication or vaccination. Another alternative approach is to prevent diseases by improving the immune capacity of fish by or genetic selection. Selection breeding has made a great progress for common carp, but only limited to the growth characteristics, and resistance breeding research was only in the initial stage. In the future, common carp industry should focus on using of genetic variation, choosing suitable breeding methods, developing diseases resistance breeding program actively. In this review, stress effects on diseases resistance, genetic basis of diseases resistance, relationship between diseases

  5. Genetic dissection of chlorophyll content at different growth stages in common wheat

    Indian Academy of Sciences (India)

    Kunpu Zhang; Zhijun Fang; Yan Liang; Jichun Tian

    2009-08-01

    Quantitative trait loci (QTLs) for chlorophyll content were studied using a doubled haploid (DH) population with 168 progeny lines, derived from a cross between two elite Chinese wheat cultivars Huapei 3 × Yumai 57. Chlorophyll content was evaluated at the maximum tillering stage (MS), the heading stage (HS), and the grain filling stage (GS), at three different environments in 2005 and 2006 cropping seasons. QTL analyses were performed using a mixed linear model approach. A total of 17 additive QTLs and nine pairs of epistatic QTLs were detected. Ten of 17 additive QTLs for chlorophyll content were persistently expressed at more than two growth stages, which suggest developmentally regulated loci controlling genetics for chlorophyll content in different growth stages in wheat. One novel major QTL for chlorophyll content was closely linked with the PCR marker Xwmc215 and was persistently expressed at three growth stages.

  6. metabolicMine: an integrated genomics, genetics and proteomics data warehouse for common metabolic disease research.

    Science.gov (United States)

    Lyne, Mike; Smith, Richard N; Lyne, Rachel; Aleksic, Jelena; Hu, Fengyuan; Kalderimis, Alex; Stepan, Radek; Micklem, Gos

    2013-01-01

    Common metabolic and endocrine diseases such as diabetes affect millions of people worldwide and have a major health impact, frequently leading to complications and mortality. In a search for better prevention and treatment, there is ongoing research into the underlying molecular and genetic bases of these complex human diseases, as well as into the links with risk factors such as obesity. Although an increasing number of relevant genomic and proteomic data sets have become available, the quantity and diversity of the data make their efficient exploitation challenging. Here, we present metabolicMine, a data warehouse with a specific focus on the genomics, genetics and proteomics of common metabolic diseases. Developed in collaboration with leading UK metabolic disease groups, metabolicMine integrates data sets from a range of experiments and model organisms alongside tools for exploring them. The current version brings together information covering genes, proteins, orthologues, interactions, gene expression, pathways, ontologies, diseases, genome-wide association studies and single nucleotide polymorphisms. Although the emphasis is on human data, key data sets from mouse and rat are included. These are complemented by interoperation with the RatMine rat genomics database, with a corresponding mouse version under development by the Mouse Genome Informatics (MGI) group. The web interface contains a number of features including keyword search, a library of Search Forms, the QueryBuilder and list analysis tools. This provides researchers with many different ways to analyse, view and flexibly export data. Programming interfaces and automatic code generation in several languages are supported, and many of the features of the web interface are available through web services. The combination of diverse data sets integrated with analysis tools and a powerful query system makes metabolicMine a valuable research resource. The web interface makes it accessible to first

  7. A model for family-based case–control studies of genetic imprinting and epistasis

    Science.gov (United States)

    Li, Xin; Sui, Yihan; Liu, Tian; Wang, Jianxin; Li, Yongci; Lin, Zhenwu; Hegarty, John; Koltun, Walter A.; Wang, Zuoheng

    2014-01-01

    Genetic imprinting, or called the parent-of-origin effect, has been recognized to play an important role in the formation and pathogenesis of human diseases. Although the epigenetic mechanisms that establish genetic imprinting have been a focus of many genetic studies, our knowledge about the number of imprinting genes and their chromosomal locations and interactions with other genes is still scarce, limiting precise inference of the genetic architecture of complex diseases. In this article, we present a statistical model for testing and estimating the effects of genetic imprinting on complex diseases using a commonly used case–control design with family structure. For each subject sampled from a case and control population, we not only genotype its own single nucleotide polymorphisms (SNPs) but also collect its parents’ genotypes. By tracing the transmission pattern of SNP alleles from parental to offspring generation, the model allows the characterization of genetic imprinting effects based on Pearson tests of a 2 × 2 contingency table. The model is expanded to test the interactions between imprinting effects and additive, dominant and epistatic effects in a complex web of genetic interactions. Statistical properties of the model are investigated, and its practical usefulness is validated by a real data analysis. The model will provide a useful tool for genome-wide association studies aimed to elucidate the picture of genetic control over complex human diseases. PMID:23887693

  8. Genetic control of the alternative pathway of complement in humans and age-related macular degeneration.

    Science.gov (United States)

    Hecker, Laura A; Edwards, Albert O; Ryu, Euijung; Tosakulwong, Nirubol; Baratz, Keith H; Brown, William L; Charbel Issa, Peter; Scholl, Hendrik P; Pollok-Kopp, Beatrix; Schmid-Kubista, Katharina E; Bailey, Kent R; Oppermann, Martin

    2010-01-01

    Activation of the alternative pathway of complement is implicated in common neurodegenerative diseases including age-related macular degeneration (AMD). We explored the impact of common variation in genes encoding proteins of the alternative pathway on complement activation in human blood and in AMD. Genetic variation across the genes encoding complement factor H (CFH), factor B (CFB) and component 3 (C3) was determined. The influence of common haplotypes defining transcriptional and translational units on complement activation in blood was determined in a quantitative genomic association study. Individual haplotypes in CFH and CFB were associated with distinct and novel effects on plasma levels of precursors, regulators and activation products of the alternative pathway of complement in human blood. Further, genetic variation in CFH thought to influence cell surface regulation of complement did not alter plasma complement levels in human blood. Plasma markers of chronic activation (split-products Ba and C3d) and an activating enzyme (factor D) were elevated in AMD subjects. Most of the elevation in AMD was accounted for by the genetic variation controlling complement activation in human blood. Activation of the alternative pathway of complement in blood is under genetic control and increases with age. The genetic variation associated with increased activation of complement in human blood also increased the risk of AMD. Our data are consistent with a disease model in which genetic variation in the complement system increases the risk of AMD by a combination of systemic complement activation and abnormal regulation of complement activation in local tissues.

  9. Mapping and Genetic Structure Analysis of the Anthracnose Resistance Locus Co-1HY in the Common Bean (Phaseolus vulgaris L.).

    Science.gov (United States)

    Chen, Mingli; Wu, Jing; Wang, Lanfen; Mantri, Nitin; Zhang, Xiaoyan; Zhu, Zhendong; Wang, Shumin

    2017-01-01

    Anthracnose is a destructive disease of the common bean (Phaseolus vulgaris L.). The Andean cultivar Hongyundou has been demonstrated to possess strong resistance to anthracnose race 81. To study the genetics of this resistance, the Hongyundou cultivar was crossed with a susceptible genotype Jingdou. Segregation of resistance for race 81 was assessed in the F2 population and F2:3 lines under controlled conditions. Results indicate that Hongyundou carries a single dominant gene for anthracnose resistance. An allele test by crossing Hongyundou with another resistant cultivar revealed that the resistance gene is in the Co-1 locus (therefore named Co-1HY). The physical distance between this locus and the two flanking markers was 46 kb, and this region included four candidate genes, namely, Phvul.001G243500, Phvul.001G243600, Phvul.001G243700 and Phvul.001G243800. These candidate genes encoded serine/threonine-protein kinases. Expression analysis of the four candidate genes in the resistant and susceptible cultivars under control condition and inoculated treatment revealed that all the four candidate genes are expressed at significantly higher levels in the resistant genotype than in susceptible genotype. Phvul.001G243600 and Phvul.001G243700 are expressed nearly 15-fold and 90-fold higher in the resistant genotype than in the susceptible parent before inoculation, respectively. Four candidate genes will provide useful information for further research into the resistance mechanism of anthracnose in common bean. The closely linked flanking markers identified here may be useful for transferring the resistance allele Co-1HY from Hongyundou to elite anthracnose susceptible common bean lines.

  10. Genetic association study of common mitochondrial variants on body fat mass.

    Directory of Open Access Journals (Sweden)

    Tie-Lin Yang

    Full Text Available Mitochondria play a central role in ATP production and energy metabolism. Previous studies suggest that common variants in mtDNA are associated with several common complex diseases, including obesity. To test the hypothesis that common mtDNA variants influence obesity-related phenotypes, including BMI and body fat mass, we genotyped a total of 445 mtSNPs across the whole mitochondrial genome in a large sample of 2,286 unrelated Caucasian subjects. 72 of these 445 mtSNPs passed quality control criteria, and were used for subsequent analyses. We also classified all subjects into nine common European haplogroups. Association analyses were conducted for both BMI and body fat mass with single mtSNPs and mtDNA haplogroups. Two mtSNPs, mt4823 and mt8873 were detected to be significantly associated with body fat mass, with adjusted P values of 4.94 × 10⁻³ and 4.58 × 10⁻², respectively. The minor alleles mt4823 C and mt8873 A were associated with reduced fat mass values and the effect size (β was estimated to be 3.52 and 3.18, respectively. These two mtSNPs also achieved nominally significant levels for association with BMI. For haplogroup analyses, we found that haplogroup X was strongly associated with both BMI (adjusted P = 8.31 × 10⁻³ and body fat mass (adjusted P = 5.67×10⁻⁴ Subjects classified as haplogroup X had lower BMI and fat mass values, with the β estimated to be 2.86 and 6.03, respectively. Our findings suggest that common variants in mitochondria might play a role in variations of body fat mass. Further molecular and functional studies will be needed to clarify the potential mechanism.

  11. Pleiotropy among common genetic loci identified for cardiometabolic disorders and C-reactive protein

    NARCIS (Netherlands)

    Ligthart, Symen; de Vries, Paul S.; Uitterlinden, André G.; Hofman, Albert; Franco, Oscar H.; Chasman, Daniel I.; Dehghan, Abbas; Dupuis, Josée; Barbalic, Maja; Bis, Joshua C.; Eiriksdottir, Gudny; Lu, Chen; Pellikka, Niina; Wallaschofski, Henri; Kettunen, Johannes; Henneman, Peter; Baumert, Jens; Strachan, David P.; Fuchsberger, Christian; Vitart, Veronique; Wilson, James F.; Paré, Guillaume; Naitza, Silvia; Rudock, Megan E.; Surakka, Ida; De Geus, Eco J. C.; Alizadeh, Behrooz Z.; Guralnik, Jack M. D.; Shuldiner, Alan; Tanaka, Toshiko; Zee, Robert Y. L.; Schnabel, Renate B.; Nambi, Vijay; Kavousi, Maryam; Ripatti, Samuli; Nauck, Matthias; Smith, Nicholas L.; Smith, Albert V.; Sundvall, Jouko; Scheet, Paul; Liu, Yongmei; Ruokonen, Aimo; Rose, Lynda M.; Larson, Martin G.; Hoogeveen, Ron C.; Freimer, Nelson B.; Teumer, Alexander; Tracy, Russell P.; Launer, Lenore J.; Buring, Julie E.; Yamamoto, Jennifer F.; Folsom, Aaron R.; Sijbrands, Eric J. G.; Pankow, James; Elliott, Paul; Keaney, John F.; Sun, Wei; Sarin, Antti-Pekka; Fontes, João D.; Badola, Sunita; Astor, Brad C.; Pouta, Anneli; Werda, Karl; Greiser, Karin H.; Kuss, Oliver; Schwabedissen, Henriette E. Meyer Zu; Thiery, Joachim; Jamshidi, Yalda; Nolte, Ilja M.; Soranzo, Nicole; Spector, Timothy D.; Völzke, Henry; Parker, Alexander N.; Aspelund, Thor; Bates, David; Young, Lauren; Tsui, Kim; Siscovick, David S.; Guo, Xiuqing; Rotter, Jerome I.; Uda, Manuela; Schlessinger, David; Rudan, Igor; Hicks, Andrew A.; Penninx, Brenda W.; Thorand, Barbara; Gieger, Christian; Coresh, Joe; Willemsen, Gonneke; Harris, Tamara B.; Järvelin, Marjo-Riitta; Rice, Kenneth; Radke, Dörte; Salomaa, Veikko; Van Dijk, Ko Willems; Boerwinkle, Eric; Vasan, Ramachandran S.; Ferrucci, Luigi; Gibson, Quince D.; Bandinelli, Stefania; Snieder, Harold; Boomsma, Dorret I.; Xiao, Xiangjun; Campbell, Harry; Hayward, Caroline; Pramstaller, Peter P.; Duijn, Cornelia Mvan; Peltonen, Leena; Psaty, Bruce M.; Gudnason, Vilmundur; Ridker, Paul M.; Homuth, Georg; Koenig, Wolfgang; Ballantyne, Christie M.; Witteman, Jacqueline C. M.; Benjamin, Emelia J.; Perola, Markus; Chasman., Daniel I.

    2015-01-01

    Pleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared genetic back

  12. Intelligent Controller Design for DC Motor Speed Control based on Fuzzy Logic-Genetic Algorithms Optimization

    OpenAIRE

    Boumediene ALLAOUA; Laoufi, Abdellah; Brahim GASBAOUI; Nasri, Abdelfatah; Abdessalam ABDERRAHMANI

    2008-01-01

    In this paper, an intelligent controller of the DC (Direct current) Motor drive is designed using fuzzy logic-genetic algorithms optimization. First, a controller is designed according to fuzzy rules such that the systems are fundamentally robust. To obtain the globally optimal values, parameters of the fuzzy controller are improved by genetic algorithms optimization model. Computer MATLAB work space demonstrate that the fuzzy controller associated to the genetic algorithms approach became ve...

  13. Reverse Genetics Approaches to Control Arenavirus.

    Science.gov (United States)

    Martínez-Sobrido, Luis; Cheng, Benson Yee Hin; de la Torre, Juan Carlos

    2016-01-01

    Several arenavirus cause hemorrhagic fever disease in humans and pose a significant public health problem in their endemic regions. To date, no licensed vaccines are available to combat human arenavirus infections, and anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetics approaches provides investigators with a novel and powerful approach for the investigation of the arenavirus molecular and cell biology. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription and the identification of novel anti-arenaviral drug targets without requiring the use of live forms of arenaviruses. Likewise, it is now feasible to rescue infectious arenaviruses entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify anti-arenaviral drugs and development of novel live-attenuated arenavirus vaccines. Recently, reverse genetics have also allowed the generation of tri-segmented arenaviruses expressing foreign genes, facilitating virus detection and opening the possibility of implementing live-attenuated arenavirus-based vaccine vector approaches. Likewise, the development of single-cycle infectious, reporter-expressing, arenaviruses has provided a new experimental method to study some aspects of the biology of highly pathogenic arenaviruses without the requirement of high-security biocontainment required to study HF-causing arenaviruses. In this chapter we summarize the current knowledge on arenavirus reverse genetics and the implementation of plasmid-based reverse genetics techniques for the development of arenavirus vaccines and vaccine vectors.

  14. Fuzzy Control of Chaotic System with Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    FANG Jian-an; GUO Zhao-xia; SHAO Shi-huang

    2002-01-01

    A novel approach to control the unpredictable behavior of chaotic systems is presented. The control algorithm is based on fuzzy logic control technique combined with genetic algorithm. The use of fuzzy logic allows for the implementation of human "rule-of-thumb" approach to decision making by employing linguistic variables. An improved Genetic Algorithm (GA) is used to learn to optimally select the fuzzy membership functions of the linguistic labels in the condition portion of each rule,and to automatically generate fuzzy control actions under each condition. Simulation results show that such an approach for the control of chaotic systems is both effective and robust.

  15. Robust reactor power control system design by genetic algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yoon Joon; Cho, Kyung Ho; Kim, Sin [Cheju National University, Cheju (Korea, Republic of)

    1997-12-31

    The H{sub {infinity}} robust controller for the reactor power control system is designed by use of the mixed weight sensitivity. The system is configured into the typical two-port model with which the weight functions are augmented. Since the solution depends on the weighting functions and the problem is of nonconvex, the genetic algorithm is used to determine the weighting functions. The cost function applied in the genetic algorithm permits the direct control of the power tracking performances. In addition, the actual operating constraints such as rod velocity and acceleration can be treated as design parameters. Compared with the conventional approach, the controller designed by the genetic algorithm results in the better performances with the realistic constraints. Also, it is found that the genetic algorithm could be used as an effective tool in the robust design. 4 refs., 6 figs. (Author)

  16. Common variants of OPA1 conferring genetic susceptibility to leprosy in Han Chinese from Southwest China.

    Science.gov (United States)

    Xiang, Yang-Lin; Zhang, Deng-Feng; Wang, Dong; Li, Yu-Ye; Yao, Yong-Gang

    2015-11-01

    Leprosy is an ancient chronic infection caused by Mycobacterium leprae. Onset of leprosy was highly affected by host nutritional condition and energy production, (partially) due to genomic loss and parasitic life style of M. leprae. The optic atrophy 1 (OPA1) gene plays an essential role in mitochondria, which function in cellular energy supply and innate immunity. To investigate the potential involvement of OPA1 in leprosy. We analyzed 7 common genetic variants of OPA1 in 1110 Han Chinese subjects with and without leprosy, followed by mRNA expression profiling and protein-protein interaction (PPI) network analysis. We observed positive associations between OPA1 variants rs9838374 (Pgenotypic=0.003) and rs414237 (Pgenotypic=0.002) with lepromatous leprosy. expression quantitative trait loci (eQTL) analysis showed that the leprosy-related risk allele C of rs414237 is correlated with lower OPA1 mRNA expression level. Indeed, we identified a decrease of OPA1 mRNA expression in both with patients and cellular model of leprosy. In addition, the PPI analysis showed that OPA1 protein was actively involved in the interaction network of M. leprae induced differentially expressed genes. Our results indicated that OPA1 variants confer risk of leprosy and may affect OPA1 expression, mitochondrial function and antimicrobial pathways. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Update on iron metabolism and molecular perspective of common genetic and acquired disorder, hemochromatosis.

    Science.gov (United States)

    Yun, Seongseok; Vincelette, Nicole D

    2015-07-01

    Iron is an essential component of erythropoiesis and its metabolism is tightly regulated by a variety of internal and external cues including iron storage, tissue hypoxia, inflammation and degree of erythropoiesis. There has been remarkable improvement in our understanding of the molecular mechanisms of iron metabolism past decades. The classical model of iron metabolism with iron response element/iron response protein (IRE/IRP) is now extended to include hepcidin model. Endogenous and exogenous signals funnel down to hepcidin via wide range of signaling pathways including Janus Kinase/Signal Transducer and Activator of Transcription 3 (JAK/STAT3), Bone Morphogenetic Protein/Hemojuvelin/Mothers Against Decapentaplegic Homolog (BMP/HJV/SMAD), and Von Hippel Lindau/Hypoxia-inducible factor/Erythropoietin (VHL/HIF/EPO), then relay to ferroportin, which directly regulates intra- and extracellular iron levels. The successful molecular delineation of iron metabolism further enhanced our understanding of common genetic and acquired disorder, hemochromatosis. The majority of the hereditary hemochromatosis (HH) patients are now shown to have mutations in the genes coding either upstream or downstream proteins of hepcidin, resulting in iron overload. The update on hepcidin centered mechanisms of iron metabolism and their clinical perspective in hemochromatosis will be discussed in this review.

  18. Cardioviruses Are Genetically Diverse and Cause Common Enteric Infections in South Asian Children▿

    Science.gov (United States)

    Blinkova, Olga; Kapoor, Amit; Victoria, Joseph; Jones, Morris; Wolfe, Nathan; Naeem, Asif; Shaukat, Shahzad; Sharif, Salmaan; Alam, Muhammad Masroor; Angez, Mehar; Zaidi, Sohail; Delwart, Eric L.

    2009-01-01

    Cardioviruses cause enteric infections in mice and rats which when disseminated have been associated with myocarditis, type 1 diabetes, encephalitis, and multiple sclerosis-like symptoms. Cardioviruses have also been detected at lower frequencies in other mammals. The Cardiovirus genus within the Picornaviridae family is currently made up of two viral species, Theilovirus and Encephalomyocarditis virus. Until recently, only a single strain of cardioviruses (Vilyuisk virus within the Theilovirus species) associated with a geographically restricted and prevalent encephalitis-like condition had been reported to occur in humans. A second theilovirus-related cardiovirus (Saffold virus [SAFV]) was reported in 2007 and subsequently found in respiratory secretions from children with respiratory problems and in stools of both healthy and diarrheic children. Using viral metagenomics, we identified RNA fragments related to SAFV in the stools of Pakistani and Afghani children with nonpolio acute flaccid paralysis (AFP). We sequenced three near-full-length genomes, showing the presence of divergent strains of SAFV and preliminary evidence of a distant recombination event between the ancestors of the Theiler-like viruses of rats and those of human SAFV. Further VP1 sequencing showed the presence of five new SAFV genotypes, doubling the reported genetic diversity of human and animal theiloviruses combined. Both AFP patients and healthy children in Pakistan were found to be excreting SAFV at high frequencies of 9 and 12%, respectively. Further studies are needed to examine the roles of these highly common and diverse SAFV genotypes in nonpolio AFP and other human diseases. PMID:19193786

  19. Cardioviruses are genetically diverse and cause common enteric infections in South Asian children.

    Science.gov (United States)

    Blinkova, Olga; Kapoor, Amit; Victoria, Joseph; Jones, Morris; Wolfe, Nathan; Naeem, Asif; Shaukat, Shahzad; Sharif, Salmaan; Alam, Muhammad Masroor; Angez, Mehar; Zaidi, Sohail; Delwart, Eric L

    2009-05-01

    Cardioviruses cause enteric infections in mice and rats which when disseminated have been associated with myocarditis, type 1 diabetes, encephalitis, and multiple sclerosis-like symptoms. Cardioviruses have also been detected at lower frequencies in other mammals. The Cardiovirus genus within the Picornaviridae family is currently made up of two viral species, Theilovirus and Encephalomyocarditis virus. Until recently, only a single strain of cardioviruses (Vilyuisk virus within the Theilovirus species) associated with a geographically restricted and prevalent encephalitis-like condition had been reported to occur in humans. A second theilovirus-related cardiovirus (Saffold virus [SAFV]) was reported in 2007 and subsequently found in respiratory secretions from children with respiratory problems and in stools of both healthy and diarrheic children. Using viral metagenomics, we identified RNA fragments related to SAFV in the stools of Pakistani and Afghani children with nonpolio acute flaccid paralysis (AFP). We sequenced three near-full-length genomes, showing the presence of divergent strains of SAFV and preliminary evidence of a distant recombination event between the ancestors of the Theiler-like viruses of rats and those of human SAFV. Further VP1 sequencing showed the presence of five new SAFV genotypes, doubling the reported genetic diversity of human and animal theiloviruses combined. Both AFP patients and healthy children in Pakistan were found to be excreting SAFV at high frequencies of 9 and 12%, respectively. Further studies are needed to examine the roles of these highly common and diverse SAFV genotypes in nonpolio AFP and other human diseases.

  20. Novel insights into thyroid hormones from the study of common genetic variation.

    Science.gov (United States)

    Dayan, Colin M; Panicker, Vijay

    2009-04-01

    Effects of thyroid hormones in individual tissues are determined by many factors beyond their serum levels, including local deiodination and expression and activity of thyroid hormone transporters. These effects are difficult to examine by traditional techniques, but a novel approach that exploits the existence of common genetic variants has yielded new and surprising insights. Convincing evidence indicates a role of type 1 iodothyronine deiodinase (D1) in determining the serum T(4):T(3) ratio and a role of phosphodiesterase 8B in determining TSH levels. In addition, studies of type 2 iodothyronine deiodinase (D2) variants have shown that thyroid hormones contribute to osteoarthritis and these variants influence Intelligence quotient alterations associated with iodine deficiency. Preliminary evidence suggests associations between TSH-receptor variants and fasting glucose level, D1 variants and insulin-like growth factor I production, and D2 variants and hypertension, psychological well-being and response to T(3) or T(4) treatment. Intriguingly, most of these associations are independent of serum thyroid hormone levels, which highlights the importance of local regulation of thyroid hormones in tissues. Future research might reveal novel roles for thyroid hormones in obesity, cardiovascular disease, osteoporosis and depression and could have implications for interpretation of thyroid function tests and individualization of thyroid hormone replacement therapy.

  1. Evaluating the performance of commercial whole-genome marker sets for capturing common genetic variation

    Directory of Open Access Journals (Sweden)

    Montpetit Alexandre

    2007-06-01

    Full Text Available Abstract Background New technologies have enabled genome-wide association studies to be conducted with hundreds of thousands of genotyped SNPs. Several different first-generation genome-wide panels of SNPs have been commercialized. The total amount of common genetic variation is still unknown; however, the coverage of commercial panels can be evaluated against reference population samples genotyped by the International HapMap project. Less information is available about coverage in samples from other populations. Results In this study we compare four commercial panels: the HumanHap 300 and HumanHap 550 Array Sets from the Illumina Infinium series and the Mapping 100 K and Mapping 500 K Array Sets from the Affymetrix GeneChip series. Tagging performance is compared among HapMap CEPH (CEU, Asian (JPT, CHB and Yoruba (YRI population samples. It is also evaluated in an Estonian population sample with more than 1000 individuals genotyped in two 500-kbp ENCODE regions of chromosome 2: ENr112 on 2p16.3 and ENr131 on 2p37.1. Conclusion We found that in a non-reference Caucasian population, commercial SNP panels provide levels of coverage similar to those in the HapMap CEPH population sample. We present the proportions of universal and population-specific SNPs in all the commercial platforms studied.

  2. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

    Science.gov (United States)

    Rietveld, Cornelius A.; Esko, Tõnu; Davies, Gail; Pers, Tune H.; Turley, Patrick; Benyamin, Beben; Chabris, Christopher F.; Emilsson, Valur; Johnson, Andrew D.; Lee, James J.; de Leeuw, Christiaan; Marioni, Riccardo E.; Medland, Sarah E.; Miller, Michael B.; Rostapshova, Olga; van der Lee, Sven J.; Vinkhuyzen, Anna A. E.; Amin, Najaf; Conley, Dalton; Derringer, Jaime; van Duijn, Cornelia M.; Fehrmann, Rudolf; Franke, Lude; Glaeser, Edward L.; Hansell, Narelle K.; Hayward, Caroline; Iacono, William G.; Ibrahim-Verbaas, Carla; Jaddoe, Vincent; Karjalainen, Juha; Laibson, David; Lichtenstein, Paul; Liewald, David C.; Magnusson, Patrik K. E.; Martin, Nicholas G.; McGue, Matt; McMahon, George; Pedersen, Nancy L.; Pinker, Steven; Porteous, David J.; Posthuma, Danielle; Rivadeneira, Fernando; Smith, Blair H.; Starr, John M.; Tiemeier, Henning; Timpson, Nicholas J.; Trzaskowski, Maciej; Uitterlinden, André G.; Verhulst, Frank C.; Ward, Mary E.; Wright, Margaret J.; Davey Smith, George; Deary, Ian J.; Johannesson, Magnus; Plomin, Robert; Visscher, Peter M.; Benjamin, Daniel J.; Koellinger, Philipp D.

    2014-01-01

    We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory. PMID:25201988

  3. Genetic diversity revealed by genomic-SSR and EST-SSR markers among common wheat, spelt and compactum

    Institute of Scientific and Technical Information of China (English)

    YANG Xinquan; LIU Peng; HAN Zongfu; NI Zhongfu; SUN Qixin

    2005-01-01

    In this study, two SSR molecular markers, named genomic-SSR and EST-SSR, are used to measure the genetic diversity among three hexaploid wheat populations, which include 28 common wheat ( Triticum aestivum L. ), 13 spelt ( Triticum spelta L. ),and 11 compactum ( Triticum compactum Host. ). The results show that common wheat has the highest genetic polymorphism, followed by spelt and then compactum. The mean genetic distance between the populations is higher than that within a population, and similar tendency is detected for individual genomes A, B and D. Therefore, spelt and compactum can be used as potential germplasms for wheat breeding, especially for enriching the genetic variation in genome D. As compared with spelt, the genetic diversity between common wheat and compactum is much smaller, indicating a closer consanguine relationship between these two species. Although the polymorphism revealed by EST-SSR is lower than that by genomic-SSR, it can effectively differentiate diverse genotypes as well. Together with our present results, it is concluded that EST-SSR marker is an ideal marker for assessing the genetic diversity in wheat. Meanwhile, the origin and evolution of hexaploid wheat is also analyzed and discussed.

  4. Common scab and its control in seed-potato crops

    NARCIS (Netherlands)

    Labruyere, R.E.

    1971-01-01

    In the Netherlands common scab of the potato is usually caused by Streptomyces scabies (Thaxter) Waksman et Henrici, following Corbaz's description, and rarely by other Streptomyces species. Variation in morphological and other characteristics could not be correlated with lesion types and non-pathog

  5. Common scab and its control in seed-potato crops

    NARCIS (Netherlands)

    Labruyere, R.E.

    1971-01-01

    In the Netherlands common scab of the potato is usually caused by Streptomyces scabies (Thaxter) Waksman et Henrici, following Corbaz's description, and rarely by other Streptomyces species. Variation in morphological and other characteristics

  6. Seascape genetics of a globally distributed, highly mobile marine mammal: the short-beaked common dolphin (genus Delphinus.

    Directory of Open Access Journals (Sweden)

    Ana R Amaral

    Full Text Available Identifying which factors shape the distribution of intraspecific genetic diversity is central in evolutionary and conservation biology. In the marine realm, the absence of obvious barriers to dispersal can make this task more difficult. Nevertheless, recent studies have provided valuable insights into which factors may be shaping genetic structure in the world's oceans. These studies were, however, generally conducted on marine organisms with larval dispersal. Here, using a seascape genetics approach, we show that marine productivity and sea surface temperature are correlated with genetic structure in a highly mobile, widely distributed marine mammal species, the short-beaked common dolphin. Isolation by distance also appears to influence population divergence over larger geographical scales (i.e. across different ocean basins. We suggest that the relationship between environmental variables and population structure may be caused by prey behaviour, which is believed to determine common dolphins' movement patterns and preferred associations with certain oceanographic conditions. Our study highlights the role of oceanography in shaping genetic structure of a highly mobile and widely distributed top marine predator. Thus, seascape genetic studies can potentially track the biological effects of ongoing climate-change at oceanographic interfaces and also inform marine reserve design in relation to the distribution and genetic connectivity of charismatic and ecologically important megafauna.

  7. Topology control based on quantum genetic algorithm in sensor networks

    Institute of Scientific and Technical Information of China (English)

    SUN Lijuan; GUO Jian; LU Kai; WANG Ruchuan

    2007-01-01

    Nowadays,two trends appear in the application of sensor networks in which both multi-service and quality of service (QoS)are supported.In terms of the goal of low energy consumption and high connectivity,the control on topology is crucial.The algorithm of topology control based on quantum genetic algorithm in sensor networks is proposed.An advantage of the quantum genetic algorithm over the conventional genetic algorithm is demonstrated in simulation experiments.The goals of high connectivity and low consumption of energy are reached.

  8. Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.

    Science.gov (United States)

    Dichgans, Martin; Malik, Rainer; König, Inke R; Rosand, Jonathan; Clarke, Robert; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Mitchell, Braxton D; Assimes, Themistocles L; Levi, Christopher; O'Donnell, Christopher J; Fornage, Myriam; Thorsteinsdottir, Unnur; Psaty, Bruce M; Hengstenberg, Christian; Seshadri, Sudha; Erdmann, Jeanette; Bis, Joshua C; Peters, Annette; Boncoraglio, Giorgio B; März, Winfried; Meschia, James F; Kathiresan, Sekar; Ikram, M Arfan; McPherson, Ruth; Stefansson, Kari; Sudlow, Cathie; Reilly, Muredach P; Thompson, John R; Sharma, Pankaj; Hopewell, Jemma C; Chambers, John C; Watkins, Hugh; Rothwell, Peter M; Roberts, Robert; Markus, Hugh S; Samani, Nilesh J; Farrall, Martin; Schunkert, Heribert

    2014-01-01

    Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (Pstroke (LAS) subtype. Common variants associated with CAD at Pgenetic risk of IS and particularly the LAS subtype with CAD.

  9. Common genetic determinants of intraocular pressure and primary open-angle glaucoma.

    Science.gov (United States)

    van Koolwijk, Leonieke M E; Ramdas, Wishal D; Ikram, M Kamran; Jansonius, Nomdo M; Pasutto, Francesca; Hysi, Pirro G; Macgregor, Stuart; Janssen, Sarah F; Hewitt, Alex W; Viswanathan, Ananth C; ten Brink, Jacoline B; Hosseini, S Mohsen; Amin, Najaf; Despriet, Dominiek D G; Willemse-Assink, Jacqueline J M; Kramer, Rogier; Rivadeneira, Fernando; Struchalin, Maksim; Aulchenko, Yurii S; Weisschuh, Nicole; Zenkel, Matthias; Mardin, Christian Y; Gramer, Eugen; Welge-Lüssen, Ulrich; Montgomery, Grant W; Carbonaro, Francis; Young, Terri L; Bellenguez, Céline; McGuffin, Peter; Foster, Paul J; Topouzis, Fotis; Mitchell, Paul; Wang, Jie Jin; Wong, Tien Y; Czudowska, Monika A; Hofman, Albert; Uitterlinden, Andre G; Wolfs, Roger C W; de Jong, Paulus T V M; Oostra, Ben A; Paterson, Andrew D; Mackey, David A; Bergen, Arthur A B; Reis, André; Hammond, Christopher J; Vingerling, Johannes R; Lemij, Hans G; Klaver, Caroline C W; van Duijn, Cornelia M

    2012-01-01

    Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4×10(-8)), and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6×10(-8)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p=2.4×10(-2) for rs11656696 and p=9.1×10(-4) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.

  10. Common genetic determinants of intraocular pressure and primary open-angle glaucoma.

    Directory of Open Access Journals (Sweden)

    Leonieke M E van Koolwijk

    Full Text Available Intraocular pressure (IOP is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4×10(-8, and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6×10(-8. In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases, both variants also showed evidence for association with glaucoma (p=2.4×10(-2 for rs11656696 and p=9.1×10(-4 for rs7555523. GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.

  11. Common genetic determinants of intraocular pressure and primary open-angle glaucoma.

    Directory of Open Access Journals (Sweden)

    Leonieke M E van Koolwijk

    Full Text Available Intraocular pressure (IOP is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4×10(-8, and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6×10(-8. In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases, both variants also showed evidence for association with glaucoma (p=2.4×10(-2 for rs11656696 and p=9.1×10(-4 for rs7555523. GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.

  12. Identification of Common Genetic Variants Influencing Spontaneous Dizygotic Twinning and Female Fertility.

    Science.gov (United States)

    Mbarek, Hamdi; Steinberg, Stacy; Nyholt, Dale R; Gordon, Scott D; Miller, Michael B; McRae, Allan F; Hottenga, Jouke Jan; Day, Felix R; Willemsen, Gonneke; de Geus, Eco J; Davies, Gareth E; Martin, Hilary C; Penninx, Brenda W; Jansen, Rick; McAloney, Kerrie; Vink, Jacqueline M; Kaprio, Jaakko; Plomin, Robert; Spector, Tim D; Magnusson, Patrik K; Reversade, Bruno; Harris, R Alan; Aagaard, Kjersti; Kristjansson, Ragnar P; Olafsson, Isleifur; Eyjolfsson, Gudmundur Ingi; Sigurdardottir, Olof; Iacono, William G; Lambalk, Cornelis B; Montgomery, Grant W; McGue, Matt; Ong, Ken K; Perry, John R B; Martin, Nicholas G; Stefánsson, Hreinn; Stefánsson, Kari; Boomsma, Dorret I

    2016-05-01

    Spontaneous dizygotic (DZ) twinning occurs in 1%-4% of women, with familial clustering and unknown physiological pathways and genetic origin. DZ twinning might index increased fertility and has distinct health implications for mother and child. We performed a GWAS in 1,980 mothers of spontaneous DZ twins and 12,953 control subjects. Findings were replicated in a large Icelandic cohort and tested for association across a broad range of fertility traits in women. Two SNPs were identified (rs11031006 near FSHB, p = 1.54 × 10(-9), and rs17293443 in SMAD3, p = 1.57 × 10(-8)) and replicated (p = 3 × 10(-3) and p = 1.44 × 10(-4), respectively). Based on ∼90,000 births in Iceland, the risk of a mother delivering twins increased by 18% for each copy of allele rs11031006-G and 9% for rs17293443-C. A higher polygenic risk score (PRS) for DZ twinning, calculated based on the results of the DZ twinning GWAS, was significantly associated with DZ twinning in Iceland (p = 0.001). A higher PRS was also associated with having children (p = 0.01), greater lifetime parity (p = 0.03), and earlier age at first child (p = 0.02). Allele rs11031006-G was associated with higher serum FSH levels, earlier age at menarche, earlier age at first child, higher lifetime parity, lower PCOS risk, and earlier age at menopause. Conversely, rs17293443-C was associated with later age at last child. We identified robust genetic risk variants for DZ twinning: one near FSHB and a second within SMAD3, the product of which plays an important role in gonadal responsiveness to FSH. These loci contribute to crucial aspects of reproductive capacity and health.

  13. Controls Over the Contractor Common Access Card Life Cycle

    Science.gov (United States)

    2008-10-10

    Identification System SES Senior Executive Service SPOC Service Point of Contact TASM Trusted Agent Security Manager USD (AT&L) Under...the final report by October 31, 2008. 53 Finding D. Oversight of Common Access Card Sponsors DoD CVS Service Points of Contact ( SPOCs ...authorization to approve contractor CACs. Organization of CAC Application Sites Each Service agency has an SPOC who is responsible for coordinating with

  14. Prediction of genotypic values and estimation of genetic parameters in common bean

    Directory of Open Access Journals (Sweden)

    Alisson Fernando Chiorato

    2008-06-01

    Full Text Available Eighteen common bean (Phaseolus vulgaris L. genotypes were evaluated in 25 environments of the state of São Paulo in 2001 and 2002. The estimation of genetic parameters by the Restricted Maximum Likelihood (REML and the prediction of genotypic values via Best Linear Unbiased Prediction (BLUP were obtained by software Selegen-REML/BLUP. The estimate of the broad-sense heritability was low for the grain yield (0.03, since it took individual plots into consideration and was free of the effects of interaction with years, cultivation periods and site. Nevertheless, the heritability at the level of line means across the various environments was high (0.75, allowing a high accuracy (0.87 in the selection of lines for planting in the environment mean. Among the 18 genotypes, the predicted genotypic values of nine were higher than the general mean. The genetic gain predicted with the selection of the best line, in this case line Gen 96A31 of the IAC, was 16.25%.Dezoito genótipos de feijoeiro (Phaseolus vulgaris L. foram avaliados em 25 ambientes do estado de São Paulo durante os anos de 2001 e 2002. As estimativas de parâmetros genéticos por REML e a predição de valores genotípicos via BLUP foram obtidas por meio do aplicativo computacional Selegen REML/BLUP, seguindo o modelo misto para linhagens. A estimativa da herdabilidade no sentido amplo para produção de grãos foi baixa (0,03, por ser em nível de parcelas individuais e livre dos efeitos da interação com anos, épocas e locais. No entanto, a herdabilidade ao nível de médias de linhagens ao longo dos vários ambientes foi alta (0,75, permitindo alta acurácia (0,87 na seleção de linhagens para plantio no ambiente médio. Dentre os 18 genótipos, nove apresentaram valores genotípicos preditos superiores à média geral. O ganho genético predito com a seleção da melhor linhagem, no caso, a linhagem Gen 96A31 do IAC, foi de 16,25%.

  15. Genes in new environments: genetics and evolution in biological control.

    Science.gov (United States)

    Roderick, George K; Navajas, Maria

    2003-11-01

    The availability of new genetic technologies has positioned the field of biological control as a test bed for theories in evolutionary biology and for understanding practical aspects of the release of genetically manipulated material. Purposeful introductions of pathogens, parasites, predators and herbivores, when considered as replicated semi-natural field experiments, show the unpredictable nature of biological colonization. The characteristics of organisms and their environments that determine this variation in the establishment and success of biological control can now be explored using genetic tools. Lessons from studies of classical biological control can help inform researchers and policy makers about the risks that are associated with the release of genetically modified organisms, particularly with respect to long-term evolutionary changes.

  16. Genetic and epigenetic control of RKIP transcription.

    Science.gov (United States)

    Datar, Ila; Tegegne, Hanna; Qin, Kevin; Al-Mulla, Fahd; Bitar, Milad S; Trumbly, Robert J; Yeung, Kam C

    2014-01-01

    Raf kinase inhibitory protein (RKIP) is known to modulate key signaling cascades and regulate normal physiological processes such as cellular proliferation, differentiation, and apoptosis. The expression of RKIP is found to be downregulated in several cancer metastases and the repressed RKIP expression can be reactivated on treatment with chemotherapeutic agents. RKIP is a proven tumor metastasis suppressor gene and investigating the mechanisms of transcriptional regulation of RKIP is therefore of immense clinical importance. In this review, we discuss the basal expression of RKIP in various tissues and the genetic aspects of the RKIP chromosomal locus including the structure of the RKIP promoter as well as gene regulatory elements such as enhancers. We also review the genetic and epigenetic modulation of RKIP transcription through EZH2, a component of the polycomb repressive complex 2 (PRC2) and sequence specific transcription factors (TFs) BACH1 and Snail. Emerging experimental evidence supports a unifying model in which both these TFs repress RKIP transcription in cancers by recruiting the EZH2 containing repressive complex to the proximal RKIP promoter. Finally, we review the known mechanisms employed by different types of chemotherapeutic agents to activate RKIP expression in cancer cells.

  17. Genetic control of active neural circuits

    Directory of Open Access Journals (Sweden)

    Leon Reijmers

    2009-12-01

    Full Text Available The use of molecular tools to study the neurobiology of complex behaviors has been hampered by an inability to target the desired changes to relevant groups of neurons. Specific memories and specific sensory representations are sparsely encoded by a small fraction of neurons embedded in a sea of morphologically and functionally similar cells. In this review we discuss genetics techniques that are being developed to address this difficulty. In several studies the use of promoter elements that are responsive to neural activity have been used to drive long lasting genetic alterations into neural ensembles that are activated by natural environmental stimuli. This approach has been used to examine neural activity patterns during learning and retrieval of a memory, to examine the regulation of receptor trafficking following learning and to functionally manipulate a specific memory trace. We suggest that these techniques will provide a general approach to experimentally investigate the link between patterns of environmentally activated neural firing and cognitive processes such as perception and memory.

  18. Contribution of common genetic variation to the risk of type 2 diabetes in the Mexican Mestizo population.

    Science.gov (United States)

    Gamboa-Meléndez, Marco Alberto; Huerta-Chagoya, Alicia; Moreno-Macías, Hortensia; Vázquez-Cárdenas, Paola; Ordóñez-Sánchez, María Luisa; Rodríguez-Guillén, Rosario; Riba, Laura; Rodríguez-Torres, Maribel; Guerra-García, María Teresa; Guillén-Pineda, Luz Elizabeth; Choudhry, Shweta; Del Bosque-Plata, Laura; Canizales-Quinteros, Samuel; Pérez-Ortiz, Gustavo; Escobedo-Aguirre, Fernando; Parra, Adalberto; Lerman-Garber, Israel; Aguilar-Salinas, Carlos Alberto; Tusié-Luna, María Teresa

    2012-12-01

    Several studies have identified nearly 40 different type 2 diabetes susceptibility loci, mainly in European populations, but few of them have been evaluated in the Mexican population. The aim of this study was to examine the extent to which 24 common genetic variants previously associated with type 2 diabetes are associated in Mexican Mestizos. Twenty-four single nucleotide polymorphisms (SNPs) in or near genes (KCNJ11, PPARG, TCF7L2, SLC30A8, HHEX, CDKN2A/2B, CDKAL1, IGF2BP2, ARHGEF11, JAZF1, CDC123/CAMK1D, FTO, TSPAN8/LGR5, KCNQ1, THADA, ADAMTS9, NOTCH2, NXPH1, RORA, UBQLNL, and RALGPS2) were genotyped in Mexican Mestizos. A case-control association study comprising 1,027 type 2 diabetic individuals and 990 control individuals was conducted. To account for population stratification, a panel of 104 ancestry-informative markers was analyzed. Association to type 2 diabetes was found for rs13266634 (SLC30A8), rs7923837 (HHEX), rs10811661 (CDKN2A/2B), rs4402960 (IGF2BP2), rs12779790 (CDC123/CAMK1D), and rs2237892 (KCNQ1). In addition, rs7754840 (CDKAL1) was associated in the nonobese type 2 diabetic subgroup, and for rs7903146 (TCF7L2), association was observed for early-onset type 2 diabetes. Lack of association for the rest of the variants may have resulted from insufficient power to detect smaller allele effects.

  19. Host Genetics and Environment Drive Divergent Responses of Two Resource Sharing Gall-Formers on Norway Spruce: A Common Garden Analysis.

    Directory of Open Access Journals (Sweden)

    E Petter Axelsson

    Full Text Available A central issue in the field of community genetics is the expectation that trait variation among genotypes play a defining role in structuring associated species and in forming community phenotypes. Quantifying the existence of such community phenotypes in two common garden environments also has important consequences for our understanding of gene-by-environment interactions at the community level. The existence of community phenotypes has not been evaluated in the crowns of boreal forest trees. In this study we address the influence of tree genetics on needle chemistry and genetic x environment interactions on two gall-inducing adelgid aphids (Adelges spp. and Sacchiphantes spp. that share the same elongating bud/shoot niche. We examine the hypothesis that the canopies of different genotypes of Norway spruce (Picea abies L. support different community phenotypes. Three patterns emerged. First, the two gallers show clear differences in their response to host genetics and environment. Whereas genetics significantly affected the abundance of Adelges spp. galls, Sacchiphantes spp. was predominately affected by the environment suggesting that the genetic influence is stronger in Adelges spp. Second, the among family variation in genetically controlled resistance was large, i.e. fullsib families differed as much as 10 fold in susceptibility towards Adelges spp. (0.57 to 6.2 galls/branch. Also, the distribution of chemical profiles was continuous, showing both overlap as well as examples of significant differences among fullsib families. Third, despite the predicted effects of host chemistry on galls, principal component analyses using 31 different phenolic substances showed only limited association with galls and a similarity test showed that trees with similar phenolic chemical characteristics, did not host more similar communities of gallers. Nonetheless, the large genetic variation in trait expression and clear differences in how community members

  20. [Sickle cell anemia causes varied symptoms and high morbidity. Serious prognosis in the most common genetic disease in the world].

    Science.gov (United States)

    Kjellander, Christian; Sennström, Maria K B; Stiller, Viveka; Ågren, Anna

    2015-03-03

    Sickle cell anemia is a life-threatening disease, and the most common genetic disease in the world. The prevalence of sickle cell anemia in Sweden is unknown. Sickle cell anemia is an important disease, because of its variable complications, in many medical and surgical specialties. The overview highlights common medical problems encountered in sickle cell anemia presented through a case report of a pregnant woman.

  1. Tuning of active vibration controllers for ACTEX by genetic algorithm

    Science.gov (United States)

    Kwak, Moon K.; Denoyer, Keith K.

    1999-06-01

    This paper is concerned with the optimal tuning of digitally programmable analog controllers on the ACTEX-1 smart structures flight experiment. The programmable controllers for each channel include a third order Strain Rate Feedback (SRF) controller, a fifth order SRF controller, a second order Positive Position Feedback (PPF) controller, and a fourth order PPF controller. Optimal manual tuning of several control parameters can be a difficult task even though the closed-loop control characteristics of each controller are well known. Hence, the automatic tuning of individual control parameters using Genetic Algorithms is proposed in this paper. The optimal control parameters of each control law are obtained by imposing a constraint on the closed-loop frequency response functions using the ACTEX mathematical model. The tuned control parameters are then uploaded to the ACTEX electronic control electronics and experiments on the active vibration control are carried out in space. The experimental results on ACTEX will be presented.

  2. Genomic Analysis of Storage Protein Deficiency in Genetically Related Lines of Common Bean (Phaseolus vulgaris)

    Science.gov (United States)

    Pandurangan, Sudhakar; Diapari, Marwan; Yin, Fuqiang; Munholland, Seth; Perry, Gregory E.; Chapman, B. Patrick; Huang, Shangzhi; Sparvoli, Francesca; Bollini, Roberto; Crosby, William L.; Pauls, Karl P.; Marsolais, Frédéric

    2016-01-01

    A series of genetically related lines of common bean (Phaseolus vulgaris L.) integrate a progressive deficiency in major storage proteins, the 7S globulin phaseolin and lectins. SARC1 integrates a lectin-like protein, arcelin-1 from a wild common bean accession. SMARC1N-PN1 is deficient in major lectins, including erythroagglutinating phytohemagglutinin (PHA-E) but not α-amylase inhibitor, and incorporates also a deficiency in phaseolin. SMARC1-PN1 is intermediate and shares the phaseolin deficiency. Sanilac is the parental background. To understand the genomic basis for variations in protein profiles previously determined by proteomics, the genotypes were submitted to short-fragment genome sequencing using an Illumina HiSeq 2000/2500 platform. Reads were aligned to reference sequences and subjected to de novo assembly. The results of the analyses identified polymorphisms responsible for the lack of specific storage proteins, as well as those associated with large differences in storage protein expression. SMARC1N-PN1 lacks the lectin genes pha-E and lec4-B17, and has the pseudogene pdlec1 in place of the functional pha-L gene. While the α-phaseolin gene appears absent, an approximately 20-fold decrease in β-phaseolin accumulation is associated with a single nucleotide polymorphism converting a G-box to an ACGT motif in the proximal promoter. Among residual lectins compensating for storage protein deficiency, mannose lectin FRIL and α-amylase inhibitor 1 genes are uniquely present in SMARC1N-PN1. An approximately 50-fold increase in α-amylase inhibitor like protein accumulation is associated with multiple polymorphisms introducing up to eight potential positive cis-regulatory elements in the proximal promoter specific to SMARC1N-PN1. An approximately 7-fold increase in accumulation of 11S globulin legumin is not associated with variation in proximal promoter sequence, suggesting that the identity of individual proteins involved in proteome rebalancing might

  3. Genetics and mapping of a new anthracnose resistance locus in Andean common bean Paloma.

    Science.gov (United States)

    de Lima Castro, Sandra Aparecida; Gonçalves-Vidigal, Maria Celeste; Gilio, Thiago Alexandre Santana; Lacanallo, Giselly Figueiredo; Valentini, Giseli; da Silva Ramos Martins, Vanusa; Song, Qijian; Galván, Marta Zulema; Hurtado-Gonzales, Oscar P; Pastor-Corrales, Marcial Antonio

    2017-04-18

    The Andean cultivar Paloma is resistant to Mesoamerican and Andean races of Colletotrichum lindemuthianum, the fungal pathogen that causes the destructive anthracnose disease in common bean. Remarkably, Paloma is resistant to Mesoamerican races 2047 and 3481, which are among the most virulent races of the anthracnose pathogen. Most genes conferring anthracnose resistance in common bean are overcome by these races. The genetic mapping and the relationship between the resistant Co-Pa gene of Paloma and previously characterized anthracnose resistance genes can be a great contribution for breeding programs. The inheritance of resistance studies for Paloma was performed in F2 population from the cross Paloma (resistant) × Cornell 49-242 (susceptible) inoculated with race 2047, and in F2 and F2:3 generations from the cross Paloma (resistant) × PI 207262 (susceptible) inoculated with race 3481. The results of these studies demonstrated that a single dominant gene confers the resistance in Paloma. Allelism tests performed with multiple races of C. lindemuthianum showed that the resistance gene in Paloma, provisionally named Co-Pa, is independent from the anthracnose resistance genes Co-1, Co-2, Co-3, Co-4, Co-5, Co-6, Co-12, Co-13, Co-14, Co-15 and Co-16. Bulk segregant analysis using the SNP chip BARCBean6K_3 positioned the approximate location of Co-Pa in the lower arm of chromosome Pv01. Further mapping analysis located the Co-Pa gene at a 390 kb region of Pv01 flanked by SNP markers SS82 and SS83 at a distance of 1.3 and 2.1 cM, respectively. The results presented here showed that Paloma cultivar has a new dominant gene conferring resistance to anthracnose, which is independent from those genes previously described. The linkage between the Co-Pa gene and the SS82 and SS83 SNP markers will be extremely important for marker-assisted introgression of the gene into elite cultivars in order to enhance resistance.

  4. Cofolga: a genetic algorithm for finding the common folding of two RNAs.

    Science.gov (United States)

    Taneda, Akito

    2005-04-01

    In order to predict non-coding RNA genes and functions on the basis of genome sequences, accurate secondary structure prediction is useful. Although single-sequence folding programs such as mfold have been successful, it is of great importance to develop a novel approach for further improvement of the prediction performance. In the present paper, a secondary structure prediction method based on genetic algorithm, Cofolga, is proposed. The program developed performs folding and alignment of two homologous RNAs simultaneously. Cofolga was tested with a dataset composed of 13 tRNAs, seven 5S rRNAs, five RNase P RNAs, and five SRP RNAs; as a result, it turned out that the average prediction accuracies for the tRNAs, 5S rRNAs, RNase P RNAs, and SRP RNAs obtained by Cofolga with an optimal weight factor and default parameters were 83.6, 81.8, 73.5, and 67.7%, respectively. These results were superior to those obtained by a single-sequence folding based on free-energy minimization in which corresponding average prediction accuracies were 52.4, 47.4, 57.7, and 52.3%, respectively. Cofolga has a post-processing in which a single-sequence folding is performed after fixation of a predicted common structure; this post-processing enables Cofolga to predict a structure that is present in one of two RNAs alone. The executable files of Cofolga (for Windows/Unix/Mac) can be obtained by an e-mail request.

  5. Association between common genetic variants in the opioid pathway and smoking behaviors in Chinese men.

    Science.gov (United States)

    Fang, Juan; Wang, Xiaohong; He, Bei

    2014-01-21

    There is biological evidence that the brain opioidergic system plays a critical role in the addictive properties of nicotine. The purpose of the present study was to examine the associations of single nucleotide polymorphisms (SNPs) in the genes encoding mu-opioid receptor (MOR) and the MOR-interacting proteins (including OPRM1, ARRB2, and HINT1) with smoking behaviors in Chinese men. A total of 284 subjects (including current and ex-smokers) were recruited. Special questionnaires were used to assess smoking behaviors including age of smoking initiation, daily cigarette consumption, and Fagerström test for nicotine dependence (FTND) score. Participant samples were genotyped for six SNPs in the opioid pathway genes: rs1799971 in OPRM1, rs1045280, rs2036657 and rs3786047 in ARRB2, rs3852209 and rs2278060 in HINT1. Linear and logistic regression models were used to determine single-locus and haplotype-based association analyses. There was no significant association between any of SNPs analyzed and smoking behaviors. Logistic regression analyses under dominant, recessive, and additive models showed no significant associations of the six SNPs with smoking status (current vs. ex-smokers). After adjustment for age at enrollment and smoking initiation age, HINT1 rs3852209 was significantly associated with smoking status with an OR of 0.54 (95% CI, 0.31-0.95; P = 0.03) under dominant inheritance model. No haplotypes in ARRB2 or HINT1 were related to smoking status. The present study indicates no significant association between common genetic variations in MOR and MOR-interacting proteins and smoking behaviors in Chinese men, and gives suggestive evidence that HINT1 rs3852209 may be related to smoking status. The findings require confirmation from further studies in additional larger samples.

  6. Genetic Control of Meat Quality Traits

    Science.gov (United States)

    Williams, John L.

    Meat was originally produced from non-specialized animals that were used for a variety of purposes, in addition to being a source of food. However, selective breeding has resulted in “improved” breeds of cattle that are now used to produce either milk or beef, and specialized chicken lines that produce eggs or meat. These improved breeds are very productive under appropriate management systems. The selection methods used to create these specialized breeds were based on easily measured phenotypic variations, such as growth rate or physical size. Improvement in the desired trait was achieved by breeding directly from animals displaying the desired phenotype. However, more recently sophisticated genetic models have been developed using statistical approaches that consider phenotypic information collected, not only from individual animals but also from their parents, sibs, and progeny.

  7. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteraceae).

    Science.gov (United States)

    Vijverberg, K; Van Der Hulst, R G M; Lindhout, P; Van Dijk, P J

    2004-02-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The genus includes sexual diploid as well as apomictic polyploid, mostly triploid, plants. Apomictic Taraxacum is diplosporous, parthenogenetic, and has autonomous endosperm formation. Previous studies have indicated that these three apomixis elements are controlled by more than one locus in Taraxacum and that diplospory inherits as a dominant, monogenic trait ( Ddd; DIP). A bulked segregant analysis provided 34 AFLP markers that were linked to DIP and were, together with two microsatellite markers, used for mapping the trait. The map length was 18.6 cM and markers were found on both sides of DIP, corresponding to 5.9 and 12.7 cM, respectively. None of the markers completely co-segregated with DIP. Eight markers were selected for PCR-based marker development, of which two were successfully converted. In contrast to all other mapping studies of apomeiosis to date, our results showed no evidence for suppression of recombination around the DIP locus in Taraxacum. No obvious evidence for sequence divergence between the DIP and non- DIP homologous loci was found, and no hemizygosity at the DIP locus was detected. These results may indicate that apomixis is relatively recent in Taraxacum.

  8. [Microsatellite data verify low genetic differentiation between western and eastern subspecies of the common crane Grusgrus L. (Gruidae, Aves)].

    Science.gov (United States)

    Mudrik, E A; Kashentseva, T A; Redchuk, P S; Politov, D V

    2015-01-01

    Using a set of 10 microsatellite loci (Gram-22, Gram-30, Gpa-12, Gpa-38, Gpa-39, Gj-M15, Gj-M34, Gj-4066, Gj-8077, Gj-2298) a high level of genetic variability (N(A) = 10.2, H(O) = = 0.684, H(E) = 0.728) and low genetic differentiation (F(ST) = 0.011) in the Common crane (Grus grus L.) was detected throughout its range. Genetic diversity in disputed western (G. g. grus) and eastern (G. g. lilfordi) sub- species was shown to be similar. Spatial distribution of multi-locus individual genotypes has not been revealed (R(XY) = 0.017). Despite low differentiation, subspecies and local populations of the Common crane should be considered as separate conservational units. Organization of programs for gene pool conservation and monitor- ing requires more detailed analysis based on combined analysis of various molecular markers.

  9. Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: Results of a meta-analysis

    NARCIS (Netherlands)

    J.M. Kerkhof (Hanneke); I. Meulenbelt (Ingrid); A. Gonzalez (Antonio); D.J. Hart (Deborah); A. Hofman (Albert); M. Kloppenburg (Margreet); N.E. Lane; J. Loughlin (John); M.C. Nevitt (Michael); H.A.P. Pols (Huib); F. Rivadeneira Ramirez (Fernando); E. Slagboom (Eline); T.D. Spector (Tim); L. Stolk (Lisette); A. Tsezou (Aspasia); A.G. Uitterlinden (André); A.M. Valdes (Ana Maria); J.B.J. van Meurs (Joyce); A.J. Carr (Andrew Jonathan)

    2010-01-01

    textabstractBackground: The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis.Methods: In the discovery study, the Rotterdam Study-I, 7 single nucleotide polymorphisms (SNPs) were genotyped and tested for association with hip

  10. 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…

  11. 29 CFR 779.224 - Common control in other cases.

    Science.gov (United States)

    2010-07-01

    ... discussed in §§ 779.225 through 779.235. Leased Departments, Franchise and Other Business Arrangements ... business activities with other persons or corporations. In such a case, the activities may be performed... arrangement between the parties so as to vest the control of the activities of one business in the hands...

  12. Pleiotropy among common genetic loci identified for cardiometabolic disorders and C-reactive protein

    NARCIS (Netherlands)

    S. Ligthart (Symen); P.S. de Vries (Paul); A.G. Uitterlinden (André); A. Hofman (Albert); O.H. Franco (Oscar); D.I. Chasman (Daniel); A. Dehghan (Abbas); J. Dupuis (Josée); M. Barbalic (maja); J.C. Bis (Joshua); G. Eiriksdottir (Gudny); Lu, C. (Chen); N. Pellikka (Niina); H. Wallaschofski (Henri); J. Kettunen (Johannes); Henneman, P. (Peter); J. Baumert (Jens); D.P. Strachan (David); C. Fuchsberger (Christian); V. Vitart (Veronique); J.F. Wilson (James F); Paré, G. (Guillaume); S. Naitza (Silvia); M.E. Rudock (Megan); I. Surakka (Ida); E.J.C. de Geus (Eco); B.Z. Alizadeh (Behrooz); J.M. Guralnik (Jack); A.R. Shuldiner (Alan); T. Tanaka (Toshiko); R.Y.L. Zee (Robert); R.B. Schnabel (Renate); V. Nambi (Vijay); M. Kavousi (Maryam); S. Ripatti (Samuli); M. Nauck (Matthias); Smith, N.L. (Nicholas L.); A.V. Smith (Albert Vernon); Sundvall, J. (Jouko); P. Scheet (Paul); Y. Liu (Yongmei); A. Ruokonen (Aimo); L.M. Rose (Lynda); M.G. Larson (Martin); R.C. Hoogeveen (Ron); N.B. Freimer (Nelson); A. Teumer (Alexander); R.P. Tracy (Russell); L.J. Launer (Lenore); J.E. Buring (Julie); J.F. Yamamoto (Jennifer); A.R. Folsom (Aaron); E.J.G. Sijbrands (Eric); J.S. Pankow (James); P. Elliott (Paul); J.F. Keaney (John); Sun, W. (Wei); A.-P. Sarin; M. Fontes (Michel); S. Badola (Sunita); B.C. Astor (Brad); Pouta, A. (Anneli); Werda, K. (Karl); K.H. Greiser (Karin Halina); O. Kuss (Oliver); Schwabedissen, H.E.M.Z. (Henriette E. Meyer Zu); Thiery, J. (Joachim); Y. Jamshidi (Yalda); Nolte, I.M. (Ilja M.); N. Soranzo (Nicole); T.D. Spector (Timothy); H. Völzke (Henry); A.N. Parker (Alex); T. Aspelund (Thor); Bates, D. (David); Young, L. (Lauren); K. Tsui (Kim); D.S. Siscovick (David); X. Guo (Xiuqing); Rotter, J.I. (Jerome I.); M. Uda (Manuela); D. Schlessinger; I. Rudan (Igor); A.A. Hicks (Andrew); B.W.J.H. Penninx (Brenda); B. Thorand (Barbara); C. Gieger (Christian); J. Coresh (Josef); G.A.H.M. Willemsen (Gonneke); T.B. Harris (Tamara); M.-R. Jarvelin (Marjo-Riitta); K.M. Rice (Kenneth); D. Radke (Dörte); V. Salomaa (Veikko); J.A.P. Willems van Dijk (Ko); E.A. Boerwinkle (Eric); R.S. Vasan (Ramachandran Srini); L. Ferrucci (Luigi); Q. Gibson (Quince); S. Bandinelli (Stefania); H. Snieder (Harold); D.I. Boomsma (Dorret); X. Xiao (Xiangjun); H. Campbell (Harry); C. Hayward (Caroline); P.P. Pramstaller (Peter Paul); C.M. van Duijn (Cock); L. Peltonen (Leena Johanna); B.M. Psaty (Bruce); V. Gudnason (Vilmundur); P.M. Ridker (Paul); G. Homuth (Georg); W. Koenig (Wolfgang); C. Ballantyne (Christie); J.C.M. Witteman (Jacqueline); E.J. Benjamin (Emelia); M. Perola (Markus); Chasman., D.I. (Daniel I.)

    2015-01-01

    textabstractPleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared

  13. Identifying Genetic Hotspots by Mapping Molecular Diversity of Widespread Trees: When Commonness Matters.

    Science.gov (United States)

    Souto, Cintia P; Mathiasen, Paula; Acosta, María Cristina; Quiroga, María Paula; Vidal-Russell, Romina; Echeverría, Cristian; Premoli, Andrea C

    2015-01-01

    Conservation planning requires setting priorities at the same spatial scale at which decision-making processes are undertaken considering all levels of biodiversity, but current methods for identifying biodiversity hotspots ignore its genetic component. We developed a fine-scale approach based on the definition of genetic hotspots, which have high genetic diversity and unique variants that represent their evolutionary potential and evolutionary novelties. Our hypothesis is that wide-ranging taxa with similar ecological tolerances, yet of phylogenetically independent lineages, have been and currently are shaped by ecological and evolutionary forces that result in geographically concordant genetic patterns. We mapped previously published genetic diversity and unique variants of biparentally inherited markers and chloroplast sequences for 9 species from 188 and 275 populations, respectively, of the 4 woody dominant families of the austral temperate forest, an area considered a biodiversity hotspot. Spatial distribution patterns of genetic polymorphisms differed among taxa according to their ecological tolerances. Eight genetic hotspots were detected and we recommend conservation actions for some in the southern Coastal Range in Chile. Existing spatially explicit genetic data from multiple populations and species can help to identify biodiversity hotspots and guide conservation actions to establish science-based protected areas that will preserve the evolutionary potential of key habitats and species.

  14. Common genetic variations in the CYP2R1 and GC genes are determinants of vitamin D status in Danes

    DEFF Research Database (Denmark)

    Nissen, Ioanna

    ), after 6 months intake of vitamin D3-fortified bread and milk (paper II) and in 92 participants in the VitDgen study after artificial UVB irradiation during winter (paper III). Common genetic variations in the CYP2R1 and GC genes were found to be important determinants of vitamin D status in three out...... by genetic variation in vitamin D modulating genes. Twin and family-based studies indicate that genetic variation may have an appreciable influence on vitamin D status. Moreover, several candidate gene studies including two genome-wide association studies (GWAS) have found single nucleotide polymorphisms...... (SNPs) in CYP2R1, CYP24A1, CYP27B1, C10orf88, DHCR7/NADSYN1, GC and VDR genes to be associated with vitamin D status. The main hypothesis of this work was that genetically determined variation in vitamin D metabolism would influence the effect of vitamin D sources (vitamin D...

  15. OPTIMAL-TUNING OF PID CONTROLLER GAINS USING GENETIC ALGORITHMS

    Directory of Open Access Journals (Sweden)

    Ömer GÜNDOĞDU

    2005-01-01

    Full Text Available This paper presents a method of optimum parameter tuning of a PID controller to be used in driving an inertial load by a dc motor thorough a gearbox. Specifically, the method uses genetic algorithms to determine the optimum controller parameters by minimizing the sum of the integral of the squared error and the squared controller output deviated from its steady state value. The paper suggests the use of Ziegler-Nichols settings to form the intervals for the controller parameters in which the population to be formed. The results obtained from the genetic algorithms are compared with the ones from Ziegler-Nichols in both figures and tabular form. Comparatively better results are obtained in the genetic algorithm case.

  16. Phylogeography and Conservation Genetics of the Common Wall Lizard, Podarcis muralis, on Islands at Its Northern Range

    Science.gov (United States)

    Michaelides, Sozos; Cornish, Nina; Griffiths, Richard; Groombridge, Jim; Zajac, Natalia; Walters, Graham J.; Aubret, Fabien; While, Geoffrey M.; Uller, Tobias

    2015-01-01

    Populations at range limits are often characterized by lower genetic diversity, increased genetic isolation and differentiation relative to populations at the core of geographical ranges. Furthermore, it is increasingly recognized that populations situated at range limits might be the result of human introductions rather than natural dispersal. It is therefore important to document the origin and genetic diversity of marginal populations to establish conservation priorities. In this study, we investigate the phylogeography and genetic structure of peripheral populations of the common European wall lizard, Podarcis muralis, on Jersey (Channel Islands, UK) and in the Chausey archipelago. We sequenced a fragment of the mitochondrial cytochrome b gene in 200 individuals of P. muralis to infer the phylogeography of the island populations using Bayesian approaches. We also genotyped 484 individuals from 21 populations at 10 polymorphic microsatellite loci to evaluate the genetic structure and diversity of island and mainland (Western France) populations. We detected four unique haplotypes in the island populations that formed a sub-clade within the Western France clade. There was a significant reduction in genetic diversity (HO, HE and AR) of the island populations in relation to the mainland. The small fragmented island populations at the northern range margin of the common wall lizard distribution are most likely native, with genetic differentiation reflecting isolation following sea level increase approximately 7000 BP. Genetic diversity is lower on islands than in marginal populations on the mainland, potentially as a result of early founder effects or long-term isolation. The combination of restriction to specific localities and an inability to expand their range into adjacent suitable locations might make the island populations more vulnerable to extinction. PMID:25659074

  17. Analysis of 3 common polymorphisms in the KCNK18 gene in an Australian Migraine case-control cohort.

    Science.gov (United States)

    Maher, B H; Taylor, M; Stuart, S; Okolicsanyi, R K; Roy, B; Sutherland, H G; Haupt, L M; Griffiths, L R

    2013-10-10

    Migraine is a common neurological disorder characterised by temporary disabling attacks of severe head pain and associated disturbances. There is significant evidence to suggest a genetic aetiology to the disease however few causal mutations have been conclusively linked to the migraine subtypes Migraine with (MA) or without Aura (MO). The Potassium Channel, Subfamily K, member 18 (KCNK18) gene, coding the potassium channel TRESK, is the first gene in which a rare mutation resulting in a non-functional truncated protein has been identified and causally linked to MA in a multigenerational family. In this study, three common polymorphisms in the KCNK18 gene were analysed for genetic variation in an Australian case-control migraine population consisting of 340 migraine cases and 345 controls. No association was observed for the polymorphisms examined with the migraine phenotype or with any haplotypes across the gene. Therefore even though the KCNK18 gene is the only gene to be causally linked to MA our studies indicate that common genetic variation in the gene is not a contributor to MA. © 2013.

  18. Phenotype-Based Genetic Association Studies (PGAS)-Towards Understanding the Contribution of Common Genetic Variants to Schizophrenia Subphenotypes.

    Science.gov (United States)

    Ehrenreich, Hannelore; Nave, Klaus-Armin

    2014-02-27

    Neuropsychiatric diseases ranging from schizophrenia to affective disorders and autism are heritable, highly complex and heterogeneous conditions, diagnosed purely clinically, with no supporting biomarkers or neuroimaging criteria. Relying on these "umbrella diagnoses", genetic analyses, including genome-wide association studies (GWAS), were undertaken but failed to provide insight into the biological basis of these disorders. "Risk genotypes" of unknown significance with low odds ratios of mostly definition of biological subgroups of mental diseases. For that purpose, the GRAS (Göttingen Research Association for Schizophrenia) data collection was initiated in 2005. With >3000 phenotypical data points per patient, it comprises the world-wide largest currently available schizophrenia database (N > 1200), combining genome-wide SNP coverage and deep phenotyping under highly standardized conditions. First PGAS results on normal genetic variants, relevant for e.g., cognition or catatonia, demonstrated proof-of-concept. Presently, an autistic subphenotype of schizophrenia is being defined where an unfortunate accumulation of normal genotypes, so-called pro-autistic variants of synaptic genes, explains part of the phenotypical variance. Deep phenotyping and comprehensive clinical data sets, however, are expensive and it may take years before PGAS will complement conventional GWAS approaches in psychiatric genetics.

  19. Pollution and genetic structure of North American populations of the common dandelion (Taraxacum officinale).

    Science.gov (United States)

    Keane, Brian; Collier, Matthew H; Rogstad, Steven H

    2005-06-01

    Assessing the genetic structure of natural populations differentially impacted by anthropogenic contaminants can be a useful tool for evaluating the population genetic consequences of exposure to pollution. In this study, measures of genetic diversity at variable-number-tandem-repeat loci in six dandelion populations (3 urban and 3 rural) showed patterns that may have been influenced by exposure to environmental contaminants. Mean genetic similarity among individuals within a population was significantly and positively correlated with increasing levels of airborne particulate matter (< or = 10 microm, PM10) and soil concentrations of four metals (Cd, Fe, Ni and Pb). In addition, mean genetic similarity was always significantly higher at the urban sites compared to rural sites. There was a significant negative correlation between the number of genotypes at a site and increasing amounts of PM10, concentrations of five soil metals (Cd, Cu, Fe, Ni and Pb), leaf tissue levels of Fe and a significant positive correlation between the extent of clonality at a site and levels of PM10 and soil concentrations of five metals (Cd, Cu, Fe, Ni and Pb). Although, this study does not directly establish a causal link between the specific contaminants detected at the study sites and differences in genetic diversity, our data are consistent with the hypothesis that pollution-induced selection has contributed in some fashion to the lower genetic diversity found at the urban sites.

  20. Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A

    Science.gov (United States)

    Kasperavičiūtė, Dalia; Catarino, Claudia B.; Matarin, Mar; Leu, Costin; Novy, Jan; Tostevin, Anna; Leal, Bárbara; Hessel, Ellen V. S.; Hallmann, Kerstin; Hildebrand, Michael S.; Dahl, Hans-Henrik M.; Ryten, Mina; Trabzuni, Daniah; Ramasamy, Adaikalavan; Alhusaini, Saud; Doherty, Colin P.; Dorn, Thomas; Hansen, Jörg; Krämer, Günter; Steinhoff, Bernhard J.; Zumsteg, Dominik; Duncan, Susan; Kälviäinen, Reetta K.; Eriksson, Kai J.; Kantanen, Anne-Mari; Pandolfo, Massimo; Gruber-Sedlmayr, Ursula; Schlachter, Kurt; Reinthaler, Eva M.; Stogmann, Elisabeth; Zimprich, Fritz; Théâtre, Emilie; Smith, Colin; O’Brien, Terence J.; Meng Tan, K.; Petrovski, Slave; Robbiano, Angela; Paravidino, Roberta; Zara, Federico; Striano, Pasquale; Sperling, Michael R.; Buono, Russell J.; Hakonarson, Hakon; Chaves, João; Costa, Paulo P.; Silva, Berta M.; da Silva, António M.; de Graan, Pierre N. E.; Koeleman, Bobby P. C.; Becker, Albert; Schoch, Susanne; von Lehe, Marec; Reif, Philipp S.; Rosenow, Felix; Becker, Felicitas; Weber, Yvonne; Lerche, Holger; Rössler, Karl; Buchfelder, Michael; Hamer, Hajo M.; Kobow, Katja; Coras, Roland; Blumcke, Ingmar; Scheffer, Ingrid E.; Berkovic, Samuel F.; Weale, Michael E.; Delanty, Norman; Depondt, Chantal; Cavalleri, Gianpiero L.; Kunz, Wolfram S.

    2013-01-01

    Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10−9, odds ratio (A) = 1.42, 95% confidence interval: 1.26–1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures

  1. Genetic control of wiring specificity in the fly olfactory system.

    Science.gov (United States)

    Hong, Weizhe; Luo, Liqun

    2014-01-01

    Precise connections established between pre- and postsynaptic partners during development are essential for the proper function of the nervous system. The olfactory system detects a wide variety of odorants and processes the information in a precisely connected neural circuit. A common feature of the olfactory systems from insects to mammals is that the olfactory receptor neurons (ORNs) expressing the same odorant receptor make one-to-one connections with a single class of second-order olfactory projection neurons (PNs). This represents one of the most striking examples of targeting specificity in developmental neurobiology. Recent studies have uncovered central roles of transmembrane and secreted proteins in organizing this one-to-one connection specificity in the olfactory system. Here, we review recent advances in the understanding of how this wiring specificity is genetically controlled and focus on the mechanisms by which transmembrane and secreted proteins regulate different stages of the Drosophila olfactory circuit assembly in a coordinated manner. We also discuss how combinatorial coding, redundancy, and error-correcting ability could contribute to constructing a complex neural circuit in general.

  2. Genetic control of midbrain dopamine systems

    NARCIS (Netherlands)

    Smits, Simone Marije

    2005-01-01

    The midbrain dopaminergic (mDA) system, organized in the substantia nigra compacta (SNc) and ventral tegmental area (VTA), regulates movement control and behavior as highlighted by the dramatic consequences of its degeneration in Parkinson’s disease and its implications in psychiatric and affective

  3. Genetic control of flowering time in rice: integration of Mendelian genetics and genomics.

    Science.gov (United States)

    Hori, Kiyosumi; Matsubara, Kazuki; Yano, Masahiro

    2016-12-01

    Integration of previous Mendelian genetic analyses and recent molecular genomics approaches, such as linkage mapping and QTL cloning, dramatically strengthened our current understanding of genetic control of rice flowering time. Flowering time is one of the most important agronomic traits for seed production in rice (Oryza sativa L.). It is controlled mainly by genes associated with photoperiod sensitivity, particularly in short-day plants such as rice. Since the early twentieth century, rice breeders and researchers have been interested in elucidating the genetic basis of flowering time because its modification is important for regional adaptation and yield optimization. Although flowering time is a complex trait controlled by many quantitative trait loci (QTLs), classical genetic studies have shown that many associated genes are inherited in accordance with Mendelian laws. Decoding the rice genome sequence opened a new era in understanding the genetic control of flowering time on the basis of genome-wide mapping and gene cloning. Heading date 1 (Hd1) was the first flowering time QTL to be isolated using natural variation in rice. Recent accumulation of information on rice genome has facilitated the cloning of other QTLs, including those with minor effects on flowering time. This information has allowed us to rediscover some of the flowering genes that were identified by classical Mendelian genetics. The genes characterized so far, including Hd1, have been assigned to specific photoperiod pathways. In this review, we provide an overview of the studies that led to an in-depth understanding of the genetic control of flowering time in rice, and of the current state of improving and fine-tuning this trait for rice breeding.

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

    Science.gov (United States)

    Asher, G W

    2007-01-01

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

  5. Common endocrine control of body weight, reproduction, and bone mass

    Science.gov (United States)

    Takeda, Shu; Elefteriou, Florent; Karsenty, Gerard

    2003-01-01

    Bone mass is maintained constant between puberty and menopause by the balance between osteoblast and osteoclast activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a strong inhibitor of bone formation. Furthermore, intracerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay. Subsequent studies have led to the identification of hypothalamic groups of neurons involved in leptin's antiosteogenic function. In addition, those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system. Sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunted the bone loss induced by ovariectomy.

  6. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease

    NARCIS (Netherlands)

    Meurs, van J.B.J.; Pare, G.; Schwartz, S.M.; Hazra, A.; Tanaka, T.; Vermeulen, S.H.; Cotlarciuc, I.; Yuan, X.; Malarstig, A.; Bandinelli, S.; Bis, J.C.; Morn, H.; Brown, M.J.; Chen, C.; Chen, Y.D.; Clarke, R.J.; Dehghan, A.; Erdmann, J.; Ferrucci, L.; Hamsten, A.; Hofman, A.; Hunten, D.J.; Goel, A.; Johnson, A.D.; Kathiresan, S.; Kampman, E.; Kiel, D.P.; Kiemeney, L.A.; Chambers, J.C.; Kraft, P.; Lindemans, J.; McKnight, B.; Nelson, C.P.; O'Donnell, C.J.; Psaty, B.M.; Ridken, P.M.; Rivadeneira, F.; Rose, L.M.; Seedoif, U.; Siscovick, D.S.; Schunkert, H.; Selhub, J.; Ueland, P.M.; Vollenweiden, P.; Waeben, G.; Waterworth, D.M.; Watkins, H.; Witteman, J.C.M.; Heijen, den M.; Jacques, P.; Uitterlinden, A.G.; Koonet, J.S.; Rader, D.J.; Reilly, M.P.; Moose, V.; Chasman, D.I.; Samani, N.J.; Ahmadi, K.R.

    2013-01-01

    Background: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteinelowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and

  7. Genetic dissection of cardiac growth control pathways

    Science.gov (United States)

    MacLellan, W. R.; Schneider, M. D.

    2000-01-01

    Cardiac muscle cells exhibit two related but distinct modes of growth that are highly regulated during development and disease. Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle irreversibly soon after birth, following which the predominant form of growth shifts from hyperplastic to hypertrophic. Much research has focused on identifying the candidate mitogens, hypertrophic agonists, and signaling pathways that mediate these processes in isolated cells. What drives the proliferative growth of embryonic myocardium in vivo and the mechanisms by which adult cardiac myocytes hypertrophy in vivo are less clear. Efforts to answer these questions have benefited from rapid progress made in techniques to manipulate the murine genome. Complementary technologies for gain- and loss-of-function now permit a mutational analysis of these growth control pathways in vivo in the intact heart. These studies have confirmed the importance of suspected pathways, have implicated unexpected pathways as well, and have led to new paradigms for the control of cardiac growth.

  8. Genetic analysis of the response to eleven Colletotrichum lindemuthianum races in a RIL population of common bean (Phaseolus vulgaris L.).

    Science.gov (United States)

    Campa, Ana; Rodríguez-Suárez, Cristina; Giraldez, Ramón; Ferreira, Juan José

    2014-04-30

    Bean anthracnose is caused by the fungus Colletotrichum lindemuthianum (Sacc. & Magnus) Lams.- Scrib. Resistance to C. lindemuthianum in common bean (Phaseolus vulgaris L.) generally follows a qualitative mode of inheritance. The pathogen shows extensive pathogenic variation and up to 20 anthracnose resistance loci (named Co-), conferring resistance to specific races, have been described. Anthracnose resistance has generally been investigated by analyzing a limited number of isolates or races in segregating populations. In this work, we analyzed the response against eleven C. lindemuthianum races in a recombinant inbred line (RIL) common bean population derived from the cross Xana × Cornell 49242 in which a saturated linkage map was previously developed. A systematic genetic analysis was carried out to dissect the complex resistance segregations observed, which included contingency analyses, subpopulations and genetic mapping. Twenty two resistance genes were identified, some with a complementary mode of action. The Cornell 49242 genotype carries a complex cluster of resistance genes at the end of linkage group (LG) Pv11 corresponding to the previously described anthracnose resistance cluster Co-2. In this position, specific resistance genes to races 3, 6, 7, 19, 38, 39, 65, 357, 449 and 453 were identified, with one of them showing a complementary mode of action. In addition, Cornell 49242 had an independent gene on LG Pv09 showing a complementary mode of action for resistance to race 453. Resistance genes in genotype Xana were located on three regions involving LGs Pv01, Pv02 and Pv04. All resistance genes identified in Xana showed a complementary mode of action, except for two controlling resistance to races 65 and 73 located on LG Pv01, in the position of the previously described anthracnose resistance cluster Co-1. Results shown herein reveal a complex and specific interaction between bean and fungus genotypes leading to anthracnose resistance. Organization

  9. Genetics of Common Polygenic Ischaemic Stroke: Current Understanding and Future Challenges

    OpenAIRE

    Bevan, S.; Markus, HS

    2011-01-01

    Stroke is the third commonest cause of death and the major cause of adult neurological disability worldwide. While much is known about conventional risk factors such as hypertension, diabetes and incidence of smoking, these environmental factors only account for a proportion of stroke risk. Up to 50% of stroke risk can be attributed to genetic risk factors, although to date no single risk allele has been convincingly identified as contributing to this risk. Advances in the field of genetics, ...

  10. Common and rare genetic markers of lipid variation in subjects with type 2 diabetes from the ACCORD clinical trial

    Directory of Open Access Journals (Sweden)

    Skylar W. Marvel

    2017-05-01

    Full Text Available Background Individuals with type 2 diabetes are at an increased risk of cardiovascular disease. Alterations in circulating lipid levels, total cholesterol (TC, low-density lipoprotein (LDL, high-density lipoprotein (HDL, and triglycerides (TG are heritable risk factors for cardiovascular disease. Here we conduct a genome-wide association study (GWAS of common and rare variants to investigate associations with baseline lipid levels in 7,844 individuals with type 2 diabetes from the ACCORD clinical trial. Methods DNA extracted from stored blood samples from ACCORD participants were genotyped using the Affymetrix Axiom Biobank 1 Genotyping Array. After quality control and genotype imputation, association of common genetic variants (CV, defined as minor allele frequency (MAF ≥ 3%, with baseline levels of TC, LDL, HDL, and TG was tested using a linear model. Rare variant (RV associations (MAF < 3% were conducted using a suite of methods that collapse multiple RV within individual genes. Results Many statistically significant CV (p < 1 × 10−8 replicate findings in large meta-analyses in non-diabetic subjects. RV analyses also confirmed findings in other studies, whereas significant RV associations with CNOT2, HPN-AS1, and SIRPD appear to be novel (q < 0.1. Discussion Here we present findings for the largest GWAS of lipid levels in people with type 2 diabetes to date. We identified 17 statistically significant (p < 1 × 10−8 associations of CV with lipid levels in 11 genes or chromosomal regions, all of which were previously identified in meta-analyses of mostly non-diabetic cohorts. We also identified 13 associations in 11 genes based on RV, several of which represent novel findings.

  11. Common and rare genetic markers of lipid variation in subjects with type 2 diabetes from the ACCORD clinical trial.

    Science.gov (United States)

    Marvel, Skylar W; Rotroff, Daniel M; Wagner, Michael J; Buse, John B; Havener, Tammy M; McLeod, Howard L; Motsinger-Reif, Alison A

    2017-01-01

    Individuals with type 2 diabetes are at an increased risk of cardiovascular disease. Alterations in circulating lipid levels, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) are heritable risk factors for cardiovascular disease. Here we conduct a genome-wide association study (GWAS) of common and rare variants to investigate associations with baseline lipid levels in 7,844 individuals with type 2 diabetes from the ACCORD clinical trial. DNA extracted from stored blood samples from ACCORD participants were genotyped using the Affymetrix Axiom Biobank 1 Genotyping Array. After quality control and genotype imputation, association of common genetic variants (CV), defined as minor allele frequency (MAF) ≥ 3%, with baseline levels of TC, LDL, HDL, and TG was tested using a linear model. Rare variant (RV) associations (MAF < 3%) were conducted using a suite of methods that collapse multiple RV within individual genes. Many statistically significant CV (p < 1 × 10(-8)) replicate findings in large meta-analyses in non-diabetic subjects. RV analyses also confirmed findings in other studies, whereas significant RV associations with CNOT2, HPN-AS1, and SIRPD appear to be novel (q < 0.1). Here we present findings for the largest GWAS of lipid levels in people with type 2 diabetes to date. We identified 17 statistically significant (p < 1 × 10(-8)) associations of CV with lipid levels in 11 genes or chromosomal regions, all of which were previously identified in meta-analyses of mostly non-diabetic cohorts. We also identified 13 associations in 11 genes based on RV, several of which represent novel findings.

  12. Feedback Control of Turbulent Shear Flows by Genetic Programming

    CERN Document Server

    Duriez, Thomas; von Krbek, Kai; Bonnet, Jean-Paul; Cordier, Laurent; Noack, Bernd R; Segond, Marc; Abel, Markus; Gautier, Nicolas; Aider, Jean-Luc; Raibaudo, Cedric; Cuvier, Christophe; Stanislas, Michel; Debien, Antoine; Mazellier, Nicolas; Kourta, Azeddine; Brunton, Steven L

    2015-01-01

    Turbulent shear flows have triggered fundamental research in nonlinear dynamics, like transition scenarios, pattern formation and dynamical modeling. In particular, the control of nonlinear dynamics is subject of research since decades. In this publication, actuated turbulent shear flows serve as test-bed for a nonlinear feedback control strategy which can optimize an arbitrary cost function in an automatic self-learning manner. This is facilitated by genetic programming providing an analytically treatable control law. Unlike control based on PID laws or neural networks, no structure of the control law needs to be specified in advance. The strategy is first applied to low-dimensional dynamical systems featuring aspects of turbulence and for which linear control methods fail. This includes stabilizing an unstable fixed point of a nonlinearly coupled oscillator model and maximizing mixing, i.e.\\ the Lyapunov exponent, for forced Lorenz equations. For the first time, we demonstrate the applicability of genetic p...

  13. Adaptive process control using fuzzy logic and genetic algorithms

    Science.gov (United States)

    Karr, C. L.

    1993-01-01

    Researchers at the U.S. Bureau of Mines have developed adaptive process control systems in which genetic algorithms (GA's) are used to augment fuzzy logic controllers (FLC's). GA's are search algorithms that rapidly locate near-optimum solutions to a wide spectrum of problems by modeling the search procedures of natural genetics. FLC's are rule based systems that efficiently manipulate a problem environment by modeling the 'rule-of-thumb' strategy used in human decision making. Together, GA's and FLC's possess the capabilities necessary to produce powerful, efficient, and robust adaptive control systems. To perform efficiently, such control systems require a control element to manipulate the problem environment, and a learning element to adjust to the changes in the problem environment. Details of an overall adaptive control system are discussed. A specific laboratory acid-base pH system is used to demonstrate the ideas presented.

  14. Optimization of PID Controllers Using Ant Colony and Genetic Algorithms

    CERN Document Server

    Ünal, Muhammet; Topuz, Vedat; Erdal, Hasan

    2013-01-01

    Artificial neural networks, genetic algorithms and the ant colony optimization algorithm have become a highly effective tool for solving hard optimization problems. As their popularity has increased, applications of these algorithms have grown in more than equal measure. While many of the books available on these subjects only provide a cursory discussion of theory, the present book gives special emphasis to the theoretical background that is behind these algorithms and their applications. Moreover, this book introduces a novel real time control algorithm, that uses genetic algorithm and ant colony optimization algorithms for optimizing PID controller parameters. In general, the present book represents a solid survey on artificial neural networks, genetic algorithms and the ant colony optimization algorithm and introduces novel practical elements related to the application of these methods to  process system control.

  15. Genetic variability in common wheat germplasm based on coefficients of parentage

    Directory of Open Access Journals (Sweden)

    Fernanda Bered

    2002-01-01

    Full Text Available The characterization of genetic variability and an estimate of the genetic relationship among varieties are essential to any breeding program, because artificial crosses among less similar parents allow a larger segregation and the combination of different favorable alleles. Genetic variability can be evaluated in different ways, including the Coefficient of Parentage (COP, which estimates the probability of two alleles in two different individuals being identical by descent. In this study, we evaluated the degree of genetic relationship among 53 wheat genotypes, and identified the ancestor genotypes which contributed the most to the current wheat germplasm, as a prediction of the width of the genetic base of this cereal. The results revealed a mean COP of 0.07 and the formation of 22 similarity groups. The ancestor genotypes Ciano 67 and Mentana were those which contributed the most to the current wheat germplasm. According to the COP analyses, the genetic base of wheat rests on a small number of ancestral genotypes.

  16. Do common systems control eye movements and motion extrapolation?

    Science.gov (United States)

    Makin, Alexis D J; Poliakoff, Ellen

    2011-07-01

    People are able to judge the current position of occluded moving objects. This operation is known as motion extrapolation. It has previously been suggested that motion extrapolation is independent of the oculomotor system. Here we revisited this question by measuring eye position while participants completed two types of motion extrapolation task. In one task, a moving visual target travelled rightwards, disappeared, then reappeared further along its trajectory. Participants discriminated correct reappearance times from incorrect (too early or too late) with a two-alternative forced-choice button press. In the second task, the target travelled rightwards behind a visible, rectangular occluder, and participants pressed a button at the time when they judged it should reappear. In both tasks, performance was significantly different under fixation as compared to free eye movement conditions. When eye movements were permitted, eye movements during occlusion were related to participants' judgements. Finally, even when participants were required to fixate, small changes in eye position around fixation (<2°) were influenced by occluded target motion. These results all indicate that overlapping systems control eye movements and judgements on motion extrapolation tasks. This has implications for understanding the mechanism underlying motion extrapolation.

  17. Quantitative assessment of common genetic variants on FOXE1 and differentiated thyroid cancer risk.

    Directory of Open Access Journals (Sweden)

    Hongling Zhu

    Full Text Available Forkhead box E1 encodes the transcription factor FOXE1 (or TTF-2, which together with Homeobox protein NKX2-1, PAX8 and HHEX, are pivotal proteins required for thyroid gland formation, differentiation and function. Recently, genome-wide association studies have identified FOXE1 as a thyroid cancer (TC susceptibility gene in populations of European descent. After that, a number of studies reported that the rs965513, rs1867277, and rs71369530 polymorphism in FOXE1 has been implicated in TC risk. However, the causal variants remain unknown. To derive a more precise estimation of the relationship, a meta-analysis of 9,828 TC cases and 109,995 controls from 14 case-control studies was performed. Overall, significant results were observed for rs965513 (OR=1.71, 95% CI: 1.59-1.85, P<10(-5, rs1867277 (OR=1.64, 95% CI: 1.51-1.78, P<10(-5 and rs71369530 (OR=2.01, 95% CI: 1.66-2.44, P<10(-5 polymorphism. In the subgroup analysis by ethnicity, we found that rs965513 polymorphism confer high risk for Caucasians with per-allele OR of 1.80 (95% CI: 1.69-1.92, P<10(-5 compared to East Asians of 1.35 (95% CI: 1.09-1.67, P=0.006. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. In the subgroup analysis by sample size, and study design, significantly increased risks were found for the polymorphism. In conclusion, this meta-analysis demonstrated that common variations of FOXE1 are a risk factor associated with increased TC susceptibility.

  18. Differences in Common Genetic Predisposition to Ischemic Stroke by Age and Sex.

    Science.gov (United States)

    Traylor, Matthew; Rutten-Jacobs, Loes C A; Holliday, Elizabeth G; Malik, Rainer; Sudlow, Cathie; Rothwell, Peter M; Maguire, Jane M; Koblar, Simon A; Bevan, Steve; Boncoraglio, Giorgio; Dichgans, Martin; Levi, Chris; Lewis, Cathryn M; Markus, Hugh S

    2015-11-01

    Evidence from epidemiological studies points to differences in factors predisposing to stroke by age and sex. Whether these arise because of different genetic influences remained untested. Here, we use data from 4 genome-wide association data sets to study the relationship between genetic influence on stroke with both age and sex. Using genomic-relatedness-matrix restricted maximum likelihood methods, we performed 4 analyses: (1) we calculated the genetic correlation between groups divided by age and (2) by sex, (3) we calculated the heritability of age-at-stroke-onset, and (4) we evaluated the evidence that heritability of stroke is greater in women than in men. We found that genetic factors influence age at stroke onset (h2 [SE]=18.0 [6.8]; P=0.0038), with a trend toward a stronger influence in women (women: h2 [SE]=21.6 [3.5]; Men: h2 [SE]=13.9 [2.8]). Although a moderate proportion of genetic factors was shared between sexes (rG [SE]=0.68 [0.16]) and between younger and older cases (rG [SE]=0.70 [0.17]), there was evidence to suggest that there are genetic susceptibility factors that are specific to sex (P=0.037) and to younger or older groups (P=0.056), particularly for women (P=0.0068). Finally, we found a trend toward higher heritability of stroke in women although this was not significantly greater than in men (P=0.084). Our results indicate that there are genetic factors that are either unique to or have a different effect between younger and older age groups and between women and men. Performing large, well-powered genome-wide association study analyses in these groups is likely to uncover further associations. © 2015 The Authors.

  19. Genetic control of anastomosis in Podospora anserina.

    Science.gov (United States)

    Tong, Laetitia Chan Ho; Silar, Philippe; Lalucque, Hervé

    2014-09-01

    We developed a new microscopy procedure to study anastomoses in the model ascomycete Podospora anserina and compared it with the previous method involving the formation of balanced heterokaryons. Both methods showed a good correlation. Heterokaryon formation was less quantifiable, but enabled to observe very rare events. Microscopic analysis evidenced that anastomoses were greatly influence by growth conditions and were severely impaired in the IDC mutants of the PaMpk1, PaMpk2, IDC1 and PaNox1 pathways. Yet some mutants readily formed heterokaryons, albeit with a delay when compared to the wild type. We also identified IDC(821), a new mutant presenting a phenotype similar to the other IDC mutants, including lack of anastomosis. Complete genome sequencing revealed that IDC(821) was affected in the orthologue of the Neurospora crassa So gene known to control anastomosis in several other ascomycetes.

  20. Environmental Control Of A Genetic Process

    Science.gov (United States)

    Khosla, Chaitan; Bailey, James E.

    1991-01-01

    E. coli bacteria altered to contain DNA sequence encoding production of hemoglobin made to produce hemoglobin at rates decreasing with increases in concentration of oxygen in culture media. Represents amplification of part of method described in "Cloned Hemoglobin Genes Enhance Growth Of Cells" (NPO-17517). Manipulation of promoter/regulator DNA sequences opens promising new subfield of recombinant-DNA technology for environmental control of expression of selected DNA sequences. New recombinant-DNA fusion gene products, expression vectors, and nucleotide-base sequences will emerge. Likely applications include such aerobic processes as manufacture of cloned proteins and synthesis of metabolites, production of chemicals by fermentation, enzymatic degradation, treatment of wastes, brewing, and variety of oxidative chemical reactions.

  1. Comparative analysis of riverscape genetic structure in rare, threatened and common freshwater mussels

    Science.gov (United States)

    Galbraith, Heather S.; Zanatta, David T; Wilson, Chris C.

    2015-01-01

    Freshwater mussels (Bivalvia: Unionoida) are highly imperiled with many species on the verge of local extirpation or global extinction. This study investigates patterns of genetic structure and diversity in six species of freshwater mussels in the central Great Lakes region of Ontario, Canada. These species vary in their conservation status (endangered to not considered at risk), life history strategy, and dispersal capabilities. Evidence of historical genetic connectivity within rivers was ubiquitous across species and may reflect dispersal abilities of host fish. There was little to no signature of recent disturbance events or bottlenecks, even in endangered species, likely as a function of mussel longevity and historical population sizes (i.e., insufficient time for genetic drift to be detectable). Genetic structure was largely at the watershed scale suggesting that population augmentation via translocation within rivers may be a useful conservation tool if needed, while minimizing genetic risks to recipient sites. Recent interest in population augmentation via translocation and propagation may rely on these results to inform management of unionids in the Great Lakes region.

  2. Human genetic variation: new challenges and opportunities for doping control.

    Science.gov (United States)

    Schneider, Angela J; Fedoruk, Matthew N; Rupert, Jim L

    2012-01-01

    Sport celebrates differences in competitors that lead to the often razor-thin margins between victory and defeat. The source of this variation is the interaction between the environment in which the athletes develop and compete and their genetic make-up. However, a darker side of sports may also be genetically influenced: some anti-doping tests are affected by the athlete's genotype. Genetic variation is an issue that anti-doping authorities must address as more is learned about the interaction between genotype and the responses to prohibited practices. To differentiate between naturally occurring deviations in indirect blood and urine markers from those potentially caused by doping, the "biological-passport" program uses intra-individual variability rather than population values to establish an athlete's expected physiological range. The next step in "personalized" doping control may be the inclusion of genetic data, both for the purposes of documenting an athlete's responses to doping agents and doping-control assays as well facilitating athlete and sample identification. Such applications could benefit "clean" athletes but will come at the expense of risks to privacy. This article reviews the instances where genetics has intersected with doping control, and briefly discusses the potential role, and ethical implications, of genotyping in the struggle to eliminate illicit ergogenic practices.

  3. Common genetic variants of surfactant protein-D (SP-D are associated with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Neus Pueyo

    Full Text Available CONTEXT: Surfactant protein-D (SP-D is a primordial component of the innate immune system intrinsically linked to metabolic pathways. We aimed to study the association of single nucleotide polymorphisms (SNPs affecting SP-D with insulin resistance and type 2 diabetes (T2D. RESEARCH DESIGN AND METHODS: We evaluated a common genetic variant located in the SP-D coding region (rs721917, Met(31Thr in a sample of T2D patients and non-diabetic controls (n = 2,711. In a subset of subjects (n = 1,062, this SNP was analyzed in association with circulating SP-D concentrations, insulin resistance, and T2D. This SNP and others were also screened in the publicly available Genome Wide Association (GWA database of the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC. RESULTS: We found the significant association of rs721917 with circulating SP-D, parameters of insulin resistance and T2D. Indeed, G carriers showed decreased circulating SP-D (p = 0.004, decreased fasting glucose (p = 0.0002, glycated hemoglobin (p = 0.0005, and 33% (p = 0.002 lower prevalence of T2D, estimated under a dominant model, especially among women. Interestingly, these differences remained significant after controlling for origin, age, gender, and circulating SP-D. Moreover, this SNP and others within the SP-D genomic region (i.e. rs10887344 were significantly associated with quantitative measures of glucose homeostasis, insulin sensitivity, and T2D, according to GWAS datasets from MAGIC. CONCLUSIONS: SP-D gene polymorphisms are associated with insulin resistance and T2D. These associations are independent of circulating SP-D concentrations.

  4. Common genetic variants and risk for HPV persistence and progression to cervical cancer.

    Directory of Open Access Journals (Sweden)

    Sophia S Wang

    Full Text Available HPV infrequently persists and progresses to cervical cancer. We examined host genetic factors hypothesized to play a role in determining which subset of individuals infected with oncogenic human papillomavirus (HPV have persistent infection and further develop cervical pre-cancer/cancer compared to the majority of infected individuals who will clear infection.We evaluated 7140 tag single nucleotide polymorphisms (SNPs from 305 candidate genes hypothesized to be involved in DNA repair, viral infection and cell entry in 416 cervical intraepithelial neoplasia 3 (CIN3/cancer cases, 356 HPV persistent women (median: 25 months, and 425 random controls (RC from the 10,049 women Guanacaste Costa Rica Natural History study. We used logistic regression to compute odds ratios and p-trend for CIN3/cancer and HPV persistence in relation to SNP genotypes and haplotypes (adjusted for age. We obtained pathway and gene-level summary of associations by computing the adaptive combination of p-values. Genes/regions statistically significantly associated with CIN3/cancer included the viral infection and cell entry genes 2',5' oligoadenylate synthetase gene 3 (OAS3, sulfatase 1 (SULF1, and interferon gamma (IFNG; the DNA repair genes deoxyuridine triphosphate (DUT, dosage suppressor of mck 1 homolog (DMC1, and general transcription factor IIH, polypeptide 3 (GTF2H4; and the EVER1 and EVER2 genes (p<0.01. From each region, the single most significant SNPs associated with CIN3/cancer were OAS3 rs12302655, SULF1 rs4737999, IFNG rs11177074, DUT rs3784621, DMC1 rs5757133, GTF2H4 rs2894054, EVER1/EVER2 rs9893818 (p-trends

  5. Epidemiology and genetics of common mental disorders in the general population: the PEGASUS-Murcia project

    Science.gov (United States)

    Navarro-Mateu, Fernando; Tormo, MJ; Vilagut, G; Alonso, J; Ruíz-Merino, G; Escámez, T; Salmerón, D; Júdez, J; Martínez, S; Navarro, C

    2013-01-01

    Background Multidisciplinary collaboration between clinicians, epidemiologists, neurogeneticists and statisticians on research projects has been encouraged to improve our knowledge of the complex mechanisms underlying the aetiology and burden of mental disorders. The PEGASUS-Murcia (Psychiatric Enquiry to General Population in Southeast Spain-Murcia) project was designed to assess the prevalence of common mental disorders and to identify the risk and protective factors, and it also included the collection of biological samples to study the gene–environmental interactions in the context of the World Mental Health Survey Initiative. Methods and analysis The PEGASUS-Murcia project is a new cross-sectional face-to-face interview survey based on a representative sample of non-institutionalised adults in the Region of Murcia (Mediterranean Southeast, Spain). Trained lay interviewers used the latest version of the computer-assisted personal interview of the Composite International Diagnostic Interview (CIDI 3.0) for use in Spain, specifically adapted for the project. Two biological samples of buccal mucosal epithelium will be collected from each interviewed participant, one for DNA extraction for genomic and epigenomic analyses and the other to obtain mRNA for gene expression quantification. Several quality control procedures will be implemented to assure the highest reliability and validity of the data. This article describes the rationale, sampling methods and questionnaire content as well as the laboratory methodology. Ethics and dissemination Informed consent will be obtained from all participants and a Regional Ethics Research Committee has approved the protocol. Results will be disseminated in peer-reviewed publications and presented at the national and the international conferences. Discussion Cross-sectional studies, which combine detailed personal information with biological data, offer new and exciting opportunities to study the gene

  6. Intelligent Controller Design for DC Motor Speed Control based on Fuzzy Logic-Genetic Algorithms Optimization

    Directory of Open Access Journals (Sweden)

    Boumediene ALLAOUA

    2008-12-01

    Full Text Available In this paper, an intelligent controller of the DC (Direct current Motor drive is designed using fuzzy logic-genetic algorithms optimization. First, a controller is designed according to fuzzy rules such that the systems are fundamentally robust. To obtain the globally optimal values, parameters of the fuzzy controller are improved by genetic algorithms optimization model. Computer MATLAB work space demonstrate that the fuzzy controller associated to the genetic algorithms approach became very strong, gives a very good results and possesses good robustness.

  7. GENETIC ALGORITHM BASED PARAMETER TUNING OF PID CONTROLLER FOR COMPOSITION CONTROL SYSTEM

    Directory of Open Access Journals (Sweden)

    Bhawna Tandon

    2011-08-01

    Full Text Available A Composition control system is discussed in this paper in which the PID controller is tuned using Genetic Algorithm & Ziegler-Nichols Tuning Criteria. Tuning methods for PID controllers are very importantfor the process industries. Traditional methods such as Ziegler-Nichols method often do not provide adequate tuning. Genetic Algorithm (GA as an intelligent approach has also been widely used to tune the parameters of PID. Genetic algorithms are used to create an objective function that can evaluate the optimum PID gains based on the controlled systems overall error.

  8. Common genetic variants in prostate cancer risk prediction – Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)

    Science.gov (United States)

    Lindström, Sara; Schumacher, Fredrick R.; Cox, David; Travis, Ruth C.; Albanes, Demetrius; Allen, Naomi E.; Andriole, Gerald; Berndt, Sonja I.; Boeing, Heiner; Bueno-de-Mesquita, H. Bas; Crawford, E. David; Diver, W. Ryan; Ganziano, J. Michael; Giles, Graham G.; Giovannucci, Edward; Gonzalez, Carlos A.; Henderson, Brian; Hunter, David J.; Johansson, Mattias; Kolonel, Laurence N.; Ma, Jing; Le Marchand, Loic; Pala, Valeria; Stampfer, Meir; Stram, Daniel O.; Thun, Michael J.; Tjonneland, Anne; Trichopoulos, Dimitrios; Virtamo, Jarmo; Weinstein, Stephanie J.; Willett, Walter C.; Yeager, Meredith; Hayes, Richard B.; Severi, Gianluca; Haiman, Christopher A.; Chanock, Stephen J.; Kraft, Peter

    2012-01-01

    Background One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent SNP markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer and age. Methods We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data. Results The best risk model (C-statistic=0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (P=0.009), with highest accuracy in men younger than 60 years (C-statistic=0.679). The absolute ten-year risk for 50-year old men with a family history ranged from 1.6% (10th percentile of genetic risk) to 6.7% (90th percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10th percentile) to 3.4% (90th percentile). Conclusions Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from PSA screening. Impact Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited. PMID:22237985

  9. [The genetic control of mouse coat color and its applications in genetics teaching].

    Science.gov (United States)

    Xing, Wanjin; Morigen, Morigen

    2014-10-01

    Mice are the most commonly used mammalian model. The coat colors of mice are typical Mendelian traits, which have various colors such as white, black, yellow and agouti. The inheritance of mouse coat color is usually stated as an example only in teaching the knowledge of recessive lethal alleles. After searched the related literatures and summarized the molecular mechanisms of mouse coat color inheritance, we further expanded the application of this example into the introduction of the basic concepts of alleles and Mendelian laws, demonstration of the gene structure and function, regulation of gene expression, gene interaction, epigenetic modification, quantitative genetics, as well as evolutionary genetics. By running this example through the whole genetics-teaching lectures, we help the student to form a systemic and developmental view of genetic analysis. At the same time, this teaching approach not only highlights the advancement and integrity of genetics, but also results in a good teaching effect on inspiring the students' interest and attracting students' attention.

  10. [Analysis of genetic diversity of Russian regional populations based on common STR markers used in DNA identification].

    Science.gov (United States)

    Pesik, V Yu; Fedunin, A A; Agdzhoyan, A T; Utevska, O M; Chukhraeva, M I; Evseeva, I V; Churnosov, M I; Lependina, I N; Bogunov, Yu V; Bogunova, A A; Ignashkin, M A; Yankovsky, N K; Balanovska, E V; Orekhov, V A; Balanovsky, O P

    2014-06-01

    We conducted the first genetic analysis of a wide a range of rural Russian populations in European Russia with a panel of common DNA markers commonly used in criminalistics genetic identification. We examined a total of 647 samples from indigenous ethnic Russian populations in Arkhangelsk, Belgorod, Voronezh, Kursk, Rostov, Ryazan, and Orel regions. We employed a multiplex genotyping kit, COrDIS Plus, to genotype Short Tandem Repeat (STR) loci, which included the genetic marker panel officially recommended for DNA identification in the Russian Federation, the United States, and the European Union. In the course of our study, we created a database of allelic frequencies, examined the distribution of alleles and genotypes in seven rural Russian populations, and defined the genetic relationships between these populations. We found that, although multidimensional analysis indicated a difference between the Northern gene pool and the rest of the Russian European populations, a pairwise comparison using 19 STR markers among all populations did not reveal significant differences. This is in concordance with previous studies, which examined up to 12 STR markers of urban Russian populations. Therefore, the database of allelic frequencies created in this study can be applied for forensic examinations and DNA identification among the ethnic Russian population over European Russia. We also noted a decrease in the levels of heterozygosity in the northern Russian population compared to ethnic populations in southern and central Russia, which is consistent with trends identified previously using classical gene markers and analysis of mitochondrial DNA.

  11. Shared genetic susceptibility to ischemic stroke and coronary artery disease – a genome-wide analysis of common variants

    Science.gov (United States)

    Dichgans, Martin; Malik, Rainer; König, Inke R.; Rosand, Jonathan; Clarke, Robert; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Mitchell, Braxton D.; Assimes, Themistocles L.; Levi, Christopher; O′Donnell, Christopher J.; Fornage, Myriam; Thorsteinsdottir, Unnur; Psaty, Bruce M.; Hengstenberg, Christian; Seshadri, Sudha; Erdmann, Jeanette; Bis, Joshua C.; Peters, Annette; Boncoraglio, Giorgio B.; März, Winfried; Meschia, James F.; Kathiresan, Sekar; Ikram, M. Arfan; McPherson, Ruth; Stefansson, Kari; Sudlow, Cathie; Reilly, Muredach P.; Thompson, John R.; Sharma, Pankaj; Hopewell, Jemma C.; Chambers, John C.; Watkins, Hugh; Rothwell, Peter M.; Roberts, Robert; Markus, Hugh S.; Samani, Nilesh J.; Farrall, Martin; Schunkert, Heribert

    2014-01-01

    Summary Background and Purpose Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each have a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. Methods Genome-wide association data were obtained from the METASTROKE, CARDIoGRAM, and C4D consortia. We first analyzed common variants reaching a nominal threshold of significance (pstroke (LAS) subtype. Results Common variants associated with CAD at pgenetic risk of ischemic stroke and particularly the large artery stroke subtype with coronary artery disease. PMID:24262325

  12. Genetic diversity, inter-gene pool introgression and nutritional quality of common beans (Phaseolus vulgaris L.) from Central Africa

    OpenAIRE

    2010-01-01

    The Great Lakes region of Central Africa is a major producer of common beans in Africa. The region is known for high population density and small average farm size. The common bean represents the most important legume crop of the region, grown on over a third of the cultivated land area, and the per capita consumption is among the highest in the world for the food crop. The objective of this study was to evaluate the genetic diversity in a collection of 365 genotypes from the Great Lakes regi...

  13. Design of PID Controller Simulator based on Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Fahri VATANSEVER

    2013-08-01

    Full Text Available PID (Proportional Integral and Derivative controllers take an important place in the field of system controlling. Various methods such as Ziegler-Nichols, Cohen-Coon, Chien Hrones Reswick (CHR and Wang-Juang-Chan are available for the design of such controllers benefiting from the system time and frequency domain data. These controllers are in compliance with system properties under certain criteria suitable to the system. Genetic algorithms have become widely used in control system applications in parallel to the advances in the field of computer and artificial intelligence. In this study, PID controller designs have been carried out by means of classical methods and genetic algorithms and comparative results have been analyzed. For this purpose, a graphical user interface program which can be used for educational purpose has been developed. For the definite (entered transfer functions, the suitable P, PI and PID controller coefficients have calculated by both classical methods and genetic algorithms and many parameters and responses of the systems have been compared and presented numerically and graphically

  14. Parameter Optimization of Linear Quadratic Controller Based on Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    LI Jimin; SHANG Chaoxuan; ZOU Minghu

    2007-01-01

    The selection of weighting matrix in design of the linear quadratic optimal controller is an important topic in the control theory. In this paper, an approach based on genetic algorithm is presented for selecting the weighting matrix for the optimal controller. Genetic algorithm is adaptive heuristic search algorithm premised on the evolutionary ideas of natural selection and genetic. In this algorithm, the fitness function is used to evaluate individuals and reproductive success varies with fitness. In the design of the linear quadratic optimal controller, the fitness function has relation to the anticipated step response of the system. Not only can the controller designed by this approach meet the demand of the performance indexes of linear quadratic controller, but also satisfy the anticipated step response of close-loop system. The method possesses a higher calculating efficiency and provides technical support for the optimal controller in engineering application. The simulation of a three-order single-input single-output (SISO) system has demonstrated the feasibility and validity of the approach.

  15. Disclosing genetic risk for coronary heart disease: effects on perceived personal control and genetic counseling satisfaction.

    Science.gov (United States)

    Robinson, C L; Jouni, H; Kruisselbrink, T M; Austin, E E; Christensen, K D; Green, R C; Kullo, I J

    2016-02-01

    We investigated whether disclosure of coronary heart disease (CHD) genetic risk influences perceived personal control (PPC) and genetic counseling satisfaction (GCS). Participants (n = 207, age: 45-65 years) were randomized to receive estimated 10-year risk of CHD based on a conventional risk score (CRS) with or without a genetic risk score (GRS). Risk estimates were disclosed by a genetic counselor who also reviewed how GRS altered risk in those randomized to CRS+GRS. Each participant subsequently met with a physician and then completed surveys to assess PPC and GCS. Participants who received CRS+GRS had higher PPC than those who received CRS alone although the absolute difference was small (25.2 ± 2.7 vs 24.1 ± 3.8, p = 0.04). A greater proportion of CRS+GRS participants had higher GCS scores (17.3 ± 5.3 vs 15.9 ± 6.3, p = 0.06). In the CRS+GRS group, PPC and GCS scores were not correlated with GRS. Within both groups, PPC and GCS scores were similar in patients with or without family history (p = NS). In conclusion, patients who received their genetic risk of CHD had higher PPC and tended to have higher GCS. Our findings suggest that disclosure of genetic risk of CHD together with conventional risk estimates is appreciated by patients. Whether this results in improved outcomes needs additional investigation.

  16. Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses

    NARCIS (Netherlands)

    Visscher, P. M.; Goddard, M. E.; Derks, E. M.; Wray, N. R.

    2012-01-01

    In this article, we review some of the data that contribute to our understanding of the genetic architecture of psychiatric disorders. These include results from evolutionary modelling (hence no data), the observed recurrence risk to relatives and data from molecular markers. We briefly discuss the

  17. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

    DEFF Research Database (Denmark)

    Jim, Heather S L; Lin, Hui-Yi; Tyrer, Jonathan P

    2015-01-01

    Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovari...

  18. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteracaea)

    NARCIS (Netherlands)

    Vijverberg, K.; Hulst, van der R.G.M.; Lindhout, W.H.; Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  19. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteraceae)

    NARCIS (Netherlands)

    Vijverberg, Kitty; van der Hulst, R.G.M.; Lindhout, P.; Van Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  20. Common Genetic Determinants of Intraocular Pressure and Primary Open-Angle Glaucoma

    NARCIS (Netherlands)

    van Koolwijk, Leonieke M. E.; Ramdas, Wishal D.; Ikram, M. Kamran; Jansonius, Nomdo M.; Pasutto, Francesca; Hysi, Pirro G.; Macgregor, Stuart; Janssen, Sarah F.; Hewitt, Alex W.; Viswanathan, Ananth C.; ten Brink, Jacoline B.; Hosseini, S. Mohsen; Amin, Najaf; Despriet, Dominiek D. G.; Willemse-Assink, Jacqueline J. M.; Kramer, Rogier; Rivadeneira, Fernando; Struchalin, Maksim; Aulchenko, Yurii S.; Weisschuh, Nicole; Zenkel, Matthias; Mardin, Christian Y.; Gramer, Eugen; Welge-Luessen, Ulrich; Montgomery, Grant W.; Carbonaro, Francis; Young, Terri L.; Bellenguez, Celine; McGuffin, Peter; Foster, Paul J.; Topouzis, Fotis; Mitchell, Paul; Wang, Jie Jin; Wong, Tien Y.; Czudowska, Monika A.; Hofman, Albert; Uitterlinden, Andre G.; Wolfs, Roger C. W.; de Jong, Paulus T. V. M.; Oostra, Ben A.; Paterson, Andrew D.; Mackey, David A.; Bergen, Arthur A. B.; Reis, Andre; Hammond, Christopher J.; Vingerling, Johannes R.; Lemij, Hans G.; Klaver, Caroline C. W.; van Duijn, Cornelia M.

    2012-01-01

    Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independen

  1. Genetic Diversity of Some Tomato Cultivars and Breeding Lines Commonly Used in Pakistani Breeding Program

    Directory of Open Access Journals (Sweden)

    Muhammad Azhar Shah

    2014-10-01

    Full Text Available Genetic diversity present in gene pool is an important determination for breeding programs, and characterization is useful of building crop plant collections primarily based on the knowledge of the presence of valuable genes and traits. Developing successful varieties for increasing the future yield and quality of tomato depend mainly on the genetic diversity of parents used in the breeding program. Molecular characterization of 21 tomato genotypes used in in Pakistani breeding program was studied using random amplified polymorphic DNA (RAPD markers. Total 102 bands were amplified among 21 genotypes using 20 RAPD primers. Overall 73.5% polymorphism was shown as 75 out of 102 loci were polymorphic. High degree of divergence between varieties was indicated by low level of monomorphic bands. The number of PCR products per primer varied from 2-8 with an average of 5.1 bands per primer. Primer GL J-20 and GL C-09 produced maximum number of bands whereas the primers GL A-09 produced the lowest. The polymorphism per RAPD primer ranged from 50% to 100% with an average of 73.5%. The accumulative analysis of amplified products generated by RAPD’s was enough to assess the genetic diversity among the genotypes. The information would be helpful for formulating future breeding and genome mapping programs. This study will also work as an indicator for tomato breeders to evolve varieties with genetic diverse back ground to achieve sustainability in tomato production in the country.

  2. Cognitive Ability, Self-Assessed Intelligence and Personality: Common Genetic but Independent Environmental Aetiologies

    Science.gov (United States)

    Bratko, Denis; Butkovic, Ana; Vukasovic, Tena; Chamorro-Premuzic, Tomas; von Stumm, Sophie

    2012-01-01

    Self-perceived abilities (SPA), which play an important role in academic achievement, have been recently reported to be fully attributable to genetic and non-shared environmental influences. To replicate and extend this finding, 732 Croatian twins (15-22 years old) were assessed on cognitive ability, self-assessed intelligence (SAI), and Five…

  3. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteracaea)

    NARCIS (Netherlands)

    Vijverberg, K.; Hulst, van der R.G.M.; Lindhout, W.H.; Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  4. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteraceae)

    NARCIS (Netherlands)

    Vijverberg, Kitty; van der Hulst, R.G.M.; Lindhout, P.; Van Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  5. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease

    NARCIS (Netherlands)

    J.B.J. van Meurs (Joyce); G. Paré (Guillaume); S.M. Schwartz (Stephen); A. Hazra (Aditi); T. Tanaka; S.H.H.M. Vermeulen (Sita); I. Cotlarciuc (Ioana); X. Yuan (Xin); A. Mälarstig (Anders); S. Bandinelli (Stefania); J.C. Bis (Joshua); H.J. Blom (Henk); M.J. Brown (Morris); C. Chen (Christopher); R. Clarke (Robert); A. Dehghan (Abbas); J. Erdmann (Jeanette); L. Ferrucci; A. Hamsten (Anders); A. Hofman (Albert); D. Hunter (David); A. Goel (Anuj); A.D. Johnson (Andrew); S. Kathiresan (Sekar); E. Kampman (Ellen); D.P. Kiel (Douglas); L.A.L.M. Kiemeney (Bart); J.C. Chambers (John); P. Kraft (Peter); J. Lindemans (Jan); B. McKnight (Barbara); C.P. Nelson (Christopher P.); C.J. O'Donnell (Christopher); B.M. Psaty (Bruce); P.M. Ridker (Paul); F. Rivadeneira Ramirez (Fernando); L.M. Rose (Lynda); U. Seedorf (Udo); D.S. Siscovick (David); H. Schunkert (Heribert); J. Selhub (Jacob); P.M. Ueland (Per); P. Vollenweider (Peter); G. Waeber (Gérard); D. Waterworth (Dawn); H. Watkins (Hugh); J.C.M. Witteman (Jacqueline); M. den Heijer (Martin); P.F. Jacques (Paul); A.G. Uitterlinden (André); J.S. Kooner (Jaspal); D.J. Rader (Daniel); M.P. Reilly (Muredach); V. Mooser (Vincent); D.I. Chasman (Daniel); N.J. Samani (Nilesh); K.R. Ahmadi (Kourosh)

    2013-01-01

    textabstractBackground: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteinelowering trials have prompted the need to identify genetic variants associated with homocysteine concen

  6. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease

    Science.gov (United States)

    The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CA...

  7. Common and different genetic background for rheumatoid arthritis and coeliac disease

    NARCIS (Netherlands)

    Coenen, Marieke J H; Trynka, Gosia; Heskamp, Sandra; Franke, Barbara; van Diemen, Cleo C; Smolonska, Joanna; van Leeuwen, Maria; Brouwer, Elisabeth; Boezen, Hendrika; Postma, Dirkje S; Platteel, Mathieu; Zanen, Pieter; Lammers, Jan-Willem W J; Groen, Hendricus; Mali, Willem P T M; Mulder, Chris J; Tack, Greetje J; Verbeek, Wieke H M; Wolters, Victorien M; Houwen, Roderick H J; Mearin, M Luisa; van Heel, David A; Radstake, Timothy R D J; van Riel, Piet L C M; Wijmenga, Cisca; Barrera, Pilar; Zhernakova, Alexandra

    2009-01-01

    Recent genome-wide association studies (GWAS) have revealed genetic risk factors in autoimmune and inflammatory disorders. Several of the associated genes and underlying pathways are shared by various autoimmune diseases. Rheumatoid arthritis (RA) and coeliac disease (CD) are two autoimmune

  8. System control fuzzy neural sewage pumping stations using genetic algorithms

    Directory of Open Access Journals (Sweden)

    Владлен Николаевич Кузнецов

    2015-06-01

    Full Text Available It is considered the system of management of sewage pumping station with regulators based on a neuron network with fuzzy logic. Linguistic rules for the controller based on fuzzy logic, maintaining the level of effluent in the receiving tank within the prescribed limits are developed. The use of genetic algorithms for neuron network training is shown.

  9. The most common genetic syndromes and associated anomalies in Latvian patients with cleft lip with or without palate.

    Science.gov (United States)

    Lace, Baiba; Barkane, Biruta; Akota, Ilze

    2006-01-01

    1 over 700 newborns every year is born with cleft lip with/or without palate, in 30% of cases there is a certain genetic mechanism underlying development of disease: chromosomal anomalies, monogenic diseases, exposure to teratogens or in utero disruptive mechanisms. The objective of our study is to describe the most common genetic syndromes and associated anomalies in patients with CL/CP in Latvia. Study material was medical records obtained from Riga Cleft Lip and Palate Centre Registry in a time period of 1980 till 2005. There was analyzed information about patients with identified genetic syndromes and associated anomalies. In a time period from 1980 till 2005, the following genetic syndromes were identified: Van der Woude, Fetal alcohol syndrome, Holzgreve syndrome, Marfan syndrome, Myotonic dystrophy, Klippel-Feil syndrome, Patau syndrome, Potter sequence and Pierre Robin sequence. 16% of CL/CP patients have recognized genetic syndromes or associated anomalies, including profound, severe and moderate mental retardation. Number is lower than expected, but still correlates with date presented in other populations. Long term follow-up of multidisciplinary specialists which includes cardiologists, clinical-geneticists and paediatricians, is needed for CL/CP patients with associated anomalies in order to identify timely side diseases and complications. Grant: Baltic-Taiwan joint research project "Identification of genes involved in craniofacial morphogenesis and susceptibility to orofacial clefting in a human genome scan 2004-2006".

  10. 26 CFR 1.52-1 - Trades or businesses that are under common control.

    Science.gov (United States)

    2010-04-01

    ... control and each uses the cash receipts and disbursements method of accounting and has a calendar year..., Corporations R and S, are a group of businesses that are under common control and each uses the cash...

  11. Range extension for the common dolphin (Delphinus sp.) to the Colombian Caribbean, with taxonomic implications from genetic barcoding and phylogenetic analyses

    Science.gov (United States)

    Chávez-Carreño, Paula Alejandra; Jiménez-Pinedo, Cristina; Palacios, Daniel M.; Caicedo, Dalila; Trujillo, Fernando; Caballero, Susana

    2017-01-01

    The nearest known population of common dolphins (Delphinus sp.) to the Colombian Caribbean occurs in a fairly restricted range in eastern Venezuela. These dolphins have not been previously reported in the Colombian Caribbean, likely because of a lack of study of the local cetacean fauna. We collected cetacean observations in waters of the Guajira Department, northern Colombia (~11°N, 73°W) during two separate efforts: (a) a seismic vessel survey (December 2009—March 2010), and (b) three coastal surveys from small boats (May—July 2012, May 2013, and May 2014). Here we document ten sightings of common dolphins collected during these surveys, which extend the known range of the species by ~1000 km into the southwestern Caribbean. We also collected nine skin biopsies in 2013 and 2014. In order to determine the taxonomic identity of the specimens, we conducted genetic barcoding and phylogenetic analyses using two mitochondrial markers, the Control Region (mtDNA) and Cytochrome b (Cytb). Results indicate that these specimens are genetically closer to the short-beaked common dolphin (Delphinus delphis) even though morphologically they resemble a long-beaked form (Delphinus sp.). However, the specific taxonomic status of common dolphins in the Caribbean and in the Western Atlantic remains unresolved. It is also unclear whether the distribution of the species between northern Colombia and eastern Venezuela is continuous or disjoined, or whether they can be considered part of the same stock. PMID:28192446

  12. Genetic improvement of tomato by targeted control of fruit softening

    KAUST Repository

    Uluisik, Selman

    2016-07-25

    Controlling the rate of softening to extend shelf life was a key target for researchers engineering genetically modified (GM) tomatoes in the 1990s, but only modest improvements were achieved. Hybrids grown nowadays contain \\'non-ripening mutations\\' that slow ripening and improve shelf life, but adversely affect flavor and color. We report substantial, targeted control of tomato softening, without affecting other aspects of ripening, by silencing a gene encoding a pectate lyase. © 2016 Nature America, Inc. All rights reserved.

  13. Genetic Algorithm based PID controller for Frequency Regulation Ancillary services

    Directory of Open Access Journals (Sweden)

    Sandeep Bhongade

    2010-12-01

    Full Text Available In this paper, the parameters of Proportional, Integral and Derivative (PID controller for Automatic Generation Control (AGC suitable in restructured power system is tuned according to Generic Algorithms (GAs based performance indices. The key idea of the proposed method is to use the fitness function based on Area Control Error (ACE. The functioning of the proposed Genetic Algorithm based PID (GAPID controller has been demonstrated on a 75-bus Indian power system network and the results have been compared with those obtained by using Least Square Minimization method.

  14. A common genetic background could explain early-onset Crohn's disease.

    Science.gov (United States)

    Bianco, Anna Monica; Zanin, Valentina; Girardelli, Martina; Magnolato, Andrea; Martelossi, Stefano; Martellossi, Stefano; Tommasini, Alberto; Marcuzzi, Annalisa; Crovella, Sergio

    2012-04-01

    Crohn's disease (CD) is a multifactorial disease, in which environmental, microbial and genetic factors play important roles. CD is characterized by a chronic granulomatous inflammation by necrotic scarring with aspects of full-thickness wall. In spite of affecting mainly young adults, sometimes, CD can be present in the first year of life (early onset Crohn disease, EOCD) showing an unpredictable course and being often more severe than at older ages. In this paper we propose the hypothesis that EOCD patients should be analyzed using a Mendelian approach with family studies aimed to identify new loci directly involved in the early onset Crohn's disease. So we will leave the classic association study approach used until now for the identification of genes responsible for susceptibility to CD and propose linkage family analysis as alternative and powerful tool for the identification of new genetic variants associated with familiar cases of EOCD.

  15. Commonalities and differences between Crohn's disease and ulcerative colitis: the genetic clues to their interpretation.

    Science.gov (United States)

    Actis, Giovanni C; Pellicano, Rinaldo; Tarallo, Sonia; Rosina, Floriano

    2011-12-01

    Traditional knowledge of clinical, laboratorial, and endoscopic orders regarding ulcerative colitis and Crohn's disease has begun to be implemented by the revolutionary data from genetic studies. Ever since many decades ago it has been clear that inflammatory bowel diseases are complex multifactorial disorders wherein gut-confined and/or environmental factors must synergize with genetic components to effect the full-blown disorder. The sequencing of the human genome and the generation of public resources of single nucleotide polymorphisms permitted the conduction of powerful population based genome-wide association studies. The latter have increased the number of the identified susceptibility loci to 99. In this review we touched on two pathways that make true susceptibility genes for inflammatory bowel diseases; gene loci that confer specific risk for ulcerative colitis and Crohn's disease were discussed in detail.

  16. Common genetic variants on 6q24 associated with exceptional episodic memory performance in the elderly

    DEFF Research Database (Denmark)

    Barral, Sandra; Cosentino, Stephanie; Christensen, Kaare;

    2014-01-01

    IMPORTANCE: There are genetic influences on memory ability as we age, but no specific genes have been identified. OBJECTIVE: To use a cognitive endophenotype, exceptional episodic memory (EEM) performance, derived from nondemented offspring from the Long Life Family Study (LLFS) to identify genetic...... variants that may be responsible for the high cognitive performance of LLFS participants and further replicate these variants using an additional 4006 nondemented individuals from 4 independent elderly cohorts. DESIGN, SETTING, AND PARTICIPANTS: A total of 467 LLFS participants from 18 families with 2...... or more offspring that exhibited exceptional memory performance were used for genome-wide linkage analysis. Adjusted multivariate linear analyses in the 40-megabase region encompassing the linkage peak were conducted using 4 independent replication data sets that included 4006 nondemented elderly...

  17. Control of Complex Systems Using Bayesian Networks and Genetic Algorithm

    CERN Document Server

    Marwala, Tshilidzi

    2007-01-01

    A method based on Bayesian neural networks and genetic algorithm is proposed to control the fermentation process. The relationship between input and output variables is modelled using Bayesian neural network that is trained using hybrid Monte Carlo method. A feedback loop based on genetic algorithm is used to change input variables so that the output variables are as close to the desired target as possible without the loss of confidence level on the prediction that the neural network gives. The proposed procedure is found to reduce the distance between the desired target and measured outputs significantly.

  18. Common Genetic Variant in VIT Is Associated with Human Brain Asymmetry

    OpenAIRE

    Tadayon, Sayed H.; Vaziri-Pashkam, Maryam; Kahali, Pegah; Ansari Dezfouli, Mitra; Abbassian, Abdolhossein

    2016-01-01

    Brain asymmetry varies across individuals. However, genetic factors contributing to this normal variation are largely unknown. Here we studied variation of cortical surface area asymmetry in a large sample of subjects. We performed principal component analysis (PCA) to capture correlated asymmetry variation across cortical regions. We found that caudal and rostral anterior cingulate together account for a substantial part of asymmetry variation among individuals. To find SNPs associated with ...

  19. Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility

    DEFF Research Database (Denmark)

    Adel Fahmideh, Maral; Lavebratt, Catharina; Schüz, Joachim

    2016-01-01

    Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain tumors (PBTs) is limited. Therefore, we investigated the association between single nucleotide polymorphisms (SNPs), identified by candidate gene-association studies on adult brain tumors, and PBT risk.The study...... cycle and DNA repair pathways variations associated with susceptibility to adult brain tumors also seem to be associated with PBT risk, suggesting pediatric and adult brain tumors might share similar etiological pathways....

  20. Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility

    DEFF Research Database (Denmark)

    Fahmideh, Maral Adel; Lavebratt, Catharina; Schüz, Joachim

    2016-01-01

    Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain tumors (PBTs) is limited. Therefore, we investigated the association between single nucleotide polymorphisms (SNPs), identified by candidate gene-association studies on adult brain tumors, and PBT risk. The study...... cycle and DNA repair pathways variations associated with susceptibility to adult brain tumors also seem to be associated with PBT risk, suggesting pediatric and adult brain tumors might share similar etiological pathways....

  1. Genetics implicate common mechanisms in autism and schizophrenia: synaptic activity and immunity.

    Science.gov (United States)

    Liu, Xiaoming; Li, Zhengwei; Fan, Conghai; Zhang, Dongli; Chen, Jiao

    2017-08-01

    The diagnosis of debilitating psychiatric disorders like autism spectrum disorder (ASD) and schizophrenia (SCHZ) is on the rise. These are severe conditions that lead to social isolation and require lifelong professional care. Improved diagnosis of ASD and SCHZ provides early access to medication and therapy, but the reality is that the mechanisms and the cellular pathology underlying these conditions are mostly unknown at this time. Although both ASD and SCHZ have strong inherited components, genetic risk seems to be distributed in hundreds of variants, each conferring low risk. The poor understanding of the genetics of ASD and SCHZ is a significant hurdle to developing effective treatments for these costly conditions. The recent implementation of next-generation sequencing technologies and the creation of large consortia have started to reveal the genetic bases of ASD and SCHZ. Alterations in gene expression regulation, synaptic architecture and activity and immunity seem to be the main cellular mechanisms contributing to both ASD and SCHZ, a surprising overlap given the distinct phenotypes and onset of these conditions. These diverse pathways seem to converge in aberrant synaptic plasticity and remodelling, which leads to altered connectivity between relevant brain regions. Continuous efforts to understand the genetic basis of ASD and SCHZ will soon lead to significant progress in the mechanistic understanding of these prominent psychiatric disorders and enable the development of disease-modifying therapies for these devastating conditions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Cryptic genetic variation can make "irreducible complexity" a common mode of adaptation in sexual populations.

    Science.gov (United States)

    Trotter, Meredith V; Weissman, Daniel B; Peterson, Grant I; Peck, Kayla M; Masel, Joanna

    2014-12-01

    The existence of complex (multiple-step) genetic adaptations that are "irreducible" (i.e., all partial combinations are less fit than the original genotype) is one of the longest standing problems in evolutionary biology. In standard genetics parlance, these adaptations require the crossing of a wide adaptive valley of deleterious intermediate stages. Here, we demonstrate, using a simple model, that evolution can cross wide valleys to produce "irreducibly complex" adaptations by making use of previously cryptic mutations. When revealed by an evolutionary capacitor, previously cryptic mutants have higher initial frequencies than do new mutations, bringing them closer to a valley-crossing saddle in allele frequency space. Moreover, simple combinatorics implies an enormous number of candidate combinations exist within available cryptic genetic variation. We model the dynamics of crossing of a wide adaptive valley after a capacitance event using both numerical simulations and analytical approximations. Although individual valley crossing events become less likely as valleys widen, by taking the combinatorics of genotype space into account, we see that revealing cryptic variation can cause the frequent evolution of complex adaptations.

  3. Genetic Algorithm Optimisation of PID Controllers for a Multivariable Process

    Directory of Open Access Journals (Sweden)

    Wael Alharbi

    2017-03-01

    Full Text Available This project is about the design of PID controllers and the improvement of outputs in multivariable processes. The optimisation of PID controller for the Shell oil process is presented in this paper, using Genetic Algorithms (GAs. Genetic Algorithms (GAs are used to automatically tune PID controllers according to given specifications. They use an objective function, which is specially formulated and measures the performance of controller in terms of time-domain bounds on the responses of closed-loop process.A specific objective function is suggested that allows the designer for a single-input, single-output (SISO process to explicitly specify the process performance specifications associated with the given problem in terms of time-domain bounds, then experimentally evaluate the closed-loop responses. This is investigated using a simple two-term parametric PID controller tuning problem. The results are then analysed and compared with those obtained using a number of popular conventional controller tuning methods. The intention is to demonstrate that the proposed objective function is inherently capable of accurately quantifying complex performance specifications in the time domain. This is something that cannot normally be employed in conventional controller design or tuning methods.Finally, the recommended objective function will be used to examine the control problems of Multi-Input-Multi-Output (MIMO processes, and the results will be presented in order to determine the efficiency of the suggested control system.

  4. Genetics of Myasthenia Gravis: A Case-Control Association Study in the Hellenic Population

    Directory of Open Access Journals (Sweden)

    Zoi Zagoriti

    2012-01-01

    Full Text Available Myasthenia gravis (MG is an heterogeneous autoimmune disease characterized by the production of autoantibodies against proteins of the postsynaptic membrane, in the neuromuscular junction. The contribution of genetic factors to MG susceptibility has been evaluated through family and twin studies however, the precise genetic background of the disease remains elusive. We conducted a case-control association study in 101 unrelated MG patients of Hellenic origin and 101 healthy volunteers in order to assess the involvement of common genetic variants in susceptibility to MG. We focused on three candidate genes which have been clearly associated with several autoimmune diseases, aiming to investigate their potential implication in MG pathogenesis. These are interferon regulatory factor 5 (IRF-5, TNFα-induced protein 3 (TNFAIP3, also known as A20, and interleukin-10 (IL-10, key molecules in the regulation of immune function. A statistical trend of association (P=0.068 between IL-10 promoter single nucleotide polymorphisms (SNPs and the subgroups of early and late-onset MG patients was revealed. No statistically significant differences were observed in the rest of the variants examined. As far as we are aware, this is the first worldwide attempt to address the possible association between IRF-5 and TNFAIP3 common genetic variants and the genetic basis of MG.

  5. Quantum control using genetic algorithms in quantum communication: superdense coding

    Science.gov (United States)

    Domínguez-Serna, Francisco; Rojas, Fernando

    2015-06-01

    We present a physical example model of how Quantum Control with genetic algorithms is applied to implement the quantum superdense code protocol. We studied a model consisting of two quantum dots with an electron with spin, including spin-orbit interaction. The electron and the spin get hybridized with the site acquiring two degrees of freedom, spin and charge. The system has tunneling and site energies as time dependent control parameters that are optimized by means of genetic algorithms to prepare a hybrid Bell-like state used as a transmission channel. This state is transformed to obtain any state of the four Bell basis as required by superdense protocol to transmit two bits of classical information. The control process protocol is equivalent to implement one of the quantum gates in the charge subsystem. Fidelities larger than 99.5% are achieved for the hybrid entangled state preparation and the superdense operations.

  6. Genetic control of organ shape and tissue polarity.

    Directory of Open Access Journals (Sweden)

    Amelia A Green

    Full Text Available The mechanisms by which genes control organ shape are poorly understood. In principle, genes may control shape by modifying local rates and/or orientations of deformation. Distinguishing between these possibilities has been difficult because of interactions between patterns, orientations, and mechanical constraints during growth. Here we show how a combination of growth analysis, molecular genetics, and modelling can be used to dissect the factors contributing to shape. Using the Snapdragon (Antirrhinum flower as an example, we show how shape development reflects local rates and orientations of tissue growth that vary spatially and temporally to form a dynamic growth field. This growth field is under the control of several dorsoventral genes that influence flower shape. The action of these genes can be modelled by assuming they modulate specified growth rates parallel or perpendicular to local orientations, established by a few key organisers of tissue polarity. Models in which dorsoventral genes only influence specified growth rates do not fully account for the observed growth fields and shapes. However, the data can be readily explained by a model in which dorsoventral genes also modify organisers of tissue polarity. In particular, genetic control of tissue polarity organisers at ventral petal junctions and distal boundaries allows both the shape and growth field of the flower to be accounted for in wild type and mutants. The results suggest that genetic control of tissue polarity organisers has played a key role in the development and evolution of shape.

  7. Tuning of a neuro-fuzzy controller by genetic algorithm.

    Science.gov (United States)

    Seng, T L; Bin Khalid, M; Yusof, R

    1999-01-01

    Due to their powerful optimization property, genetic algorithms (GAs) are currently being investigated for the development of adaptive or self-tuning fuzzy logic control systems. This paper presents a neuro-fuzzy logic controller (NFLC) where all of its parameters can be tuned simultaneously by GA. The structure of the controller is based on the radial basis function neural network (RBF) with Gaussian membership functions. The NFLC tuned by GA can somewhat eliminate laborious design steps such as manual tuning of the membership functions and selection of the fuzzy rules. The GA implementation incorporates dynamic crossover and mutation probabilistic rates for faster convergence. A flexible position coding strategy of the NFLC parameters is also implemented to obtain near optimal solutions. The performance of the proposed controller is compared with a conventional fuzzy controller and a PID controller tuned by GA. Simulation results show that the proposed controller offers encouraging advantages and has better performance.

  8. Amphibian population genetics in agricultural landscapes: does viniculture drive the population structuring of the European common frog (Rana temporaria?

    Directory of Open Access Journals (Sweden)

    Patrick P. Lenhardt

    2017-07-01

    Full Text Available Amphibian populations have been declining globally over the past decades. The intensification of agriculture, habitat loss, fragmentation of populations and toxic substances in the environment are considered as driving factors for this decline. Today, about 50% of the area of Germany is used for agriculture and is inhabited by a diverse variety of 20 amphibian species. Of these, 19 are exhibiting declining populations. Due to the protection status of native amphibian species, it is important to evaluate the effect of land use and associated stressors (such as road mortality and pesticide toxicity on the genetic population structure of amphibians in agricultural landscapes. We investigated the effects of viniculture on the genetic differentiation of European common frog (Rana temporaria populations in Southern Palatinate (Germany. We analyzed microsatellite data of ten loci from ten breeding pond populations located within viniculture landscape and in the adjacent forest block and compared these results with a previously developed landscape permeability model. We tested for significant correlation of genetic population differentiation and landscape elements, including land use as well as roads and their associated traffic intensity, to explain the genetic structure in the study area. Genetic differentiation among forest populations was significantly lower (median pairwise FST = 0.0041 at 5.39 km to 0.0159 at 9.40 km distance than between viniculture populations (median pairwise FST = 0.0215 at 2.34 km to 0.0987 at 2.39 km distance. Our analyses rejected isolation by distance based on roads and associated traffic intensity as the sole explanation of the genetic differentiation and suggest that the viniculture landscape has to be considered as a limiting barrier for R. temporaria migration, partially confirming the isolation of breeding ponds predicted by the landscape permeability model. Therefore, arable land may act as a sink habitat

  9. Sheltering behavior and locomotor activity in 11 genetically diverse common inbred mouse strains using home-cage monitoring.

    Directory of Open Access Journals (Sweden)

    Maarten Loos

    Full Text Available Functional genetic analyses in mice rely on efficient and in-depth characterization of the behavioral spectrum. Automated home-cage observation can provide a systematic and efficient screening method to detect unexplored, novel behavioral phenotypes. Here, we analyzed high-throughput automated home-cage data using existing and novel concepts, to detect a plethora of genetic differences in spontaneous behavior in a panel of commonly used inbred strains (129S1/SvImJ, A/J, C3H/HeJ, C57BL/6J, BALB/cJ, DBA/2J, NOD/LtJ, FVB/NJ, WSB/EiJ, PWK/PhJ and CAST/EiJ. Continuous video-tracking observations of sheltering behavior and locomotor activity were segmented into distinguishable behavioral elements, and studied at different time scales, yielding a set of 115 behavioral parameters of which 105 showed highly significant strain differences. This set of 115 parameters was highly dimensional; principal component analysis identified 26 orthogonal components with eigenvalues above one. Especially novel parameters of sheltering behavior and parameters describing aspects of motion of the mouse in the home-cage showed high genetic effect sizes. Multi-day habituation curves and patterns of behavior surrounding dark/light phase transitions showed striking strain differences, albeit with lower genetic effect sizes. This spontaneous home-cage behavior study demonstrates high dimensionality, with a strong genetic contribution to specific sets of behavioral measures. Importantly, spontaneous home-cage behavior analysis detects genetic effects that cannot be studied in conventional behavioral tests, showing that the inclusion of a few days of undisturbed, labor extensive home-cage assessment may greatly aid gene function analyses and drug target discovery.

  10. Genetic mapping of common bunt resistance and plant height QTL in wheat.

    Science.gov (United States)

    Singh, Arti; Knox, Ron E; DePauw, R M; Singh, A K; Cuthbert, R D; Kumar, S; Campbell, H L

    2016-02-01

    Breeding for field resistance to common bunt in wheat will need to account for multiple genes and epistatic and QTL by environment interactions. Loci associated with quantitative resistance to common bunt are co-localized with other beneficial traits including plant height and rust resistance. Common bunt, also known as stinking smut, is caused by seed borne fungi Tilletia tritici (Bjerk.) Wint. [syn. Tilletia caries (DC.) Tul.] and Tilletia laevis Kühn [syn. Tilletia foetida (Wallr.) Liro.]. Common bunt is known to cause grain yield and quality losses in wheat due to bunt ball formation and infestation of the grain. The objectives of this research were to identify and map quantitative trait loci (QTL) for common bunt resistance, to study the epistatic interactions between the identified QTL, and investigate the co-localization of bunt resistance with plant height. A population of 261 doubled haploid lines from the cross Carberry/AC Cadillac and checks were genotyped with polymorphic genome wide microsatellite and DArT(®) markers. The lines were grown in 2011, 2012, and 2013 in separate nurseries for common bunt incidence and height evaluation. AC Cadillac contributed a QTL (QCbt.spa-6D) for common bunt resistance on chromosome 6D at markers XwPt-1695, XwPt-672044, and XwPt-5114. Carberry contributed QTL for bunt resistance on chromosomes 1B (QCbt.spa-1B at XwPt743523) 4B (QCbt.spa-4B at XwPt-744434-Xwmc617), 4D (QCbt.spa-4D at XwPt-9747), 5B (QCbt.spa-5B at XtPt-3719) and 7D (QCbt.spa-7D at Xwmc273). Significant epistatic interactions were identified for percent bunt incidence between QCbt.spa-1B × QCbt.spa-4B and QCbt.spa-1B × QCbt.spa-6D, and QTL by environment interaction between QCbt.spa-1B × QCbt.spa-6D. Plant height QTL were found on chromosomes 4B (QPh.spa-4B) and 6D (QPh.spa-6D) that co-located with bunt resistance QTL. The identification of previously unreported common bunt resistance QTL (on chromosomes 4B, 4D and 7D), and new understanding of QTL

  11. Resistance of genetically different common carp, Cyprinus carpio L., families against experimental bacterial challenge with Aeromonas hydrophila.

    Science.gov (United States)

    Jeney, G; Ardó, L; Rónyai, A; Bercsényi, M; Jeney, Z

    2011-01-01

    The objective of this study was to determine the differences in disease resistance against artificial infection with Aeromonas hydrophila between genetically different common carp families. Four strains differing in their origin and breeding history were selected from the live gene bank of common carp maintained at the Research Institute for Fisheries, Aquaculture and Irrigation (HAKI, Szarvas, Hungary) to establish families with wide genetic background: Szarvas 15 (15), an inbred mirror line; Tata (T) scaly noble carp; Duna (D), a Hungarian wild carp and Amur (A), an East Asian wild carp. A diallele mating structure was used to allow the assessment of genetic variation within and between the tested 96 families for a variety of traits. The existing technologies of fertilization and incubation of carp eggs, as well as larval and fingerling rearing had been modified because of the large number of baseline populations. Two challenge trials of the 96 families of carp with Aeromonas hydrophila were done. The 10 most resistant and 10 most susceptible families to A. hydrophila were identified from these two challenges. The crosses that produced the most resistant families were mainly those having parents from Tata and Szarvas 15 domesticated strains, while the most susceptible families were from the wild strains Duna and Amur.

  12. High genetic variability in endophytic fungi from the genus Diaporthe isolated from common bean (Phaseolus vulgaris L.) in Brazil.

    Science.gov (United States)

    Dos Santos, T T; de Souza Leite, T; de Queiroz, C B; de Araújo, E F; Pereira, O L; de Queiroz, M V

    2016-02-01

    The goals of the present study were to identify, to analyse the phylogenetic relations and to evaluate the genetic variability in Diaporthe endophytic isolates from common bean. Diaporthe sp., D. infecunda and D. phaseolorum strains were identified using multilocus phylogeny (rDNA ITS region; EF1-α, β-tubulin, and calmodulin genes). IRAP (Inter-Retrotransposon Amplified Polymorphism) and REMAP (Retrotransposon-Microsatellite Amplified Polymorphism) molecular markers reveal the existence of high genetic variability, especially among D. infecunda isolates. It was concluded that the multilocus phylogenetic approach was more effective than individual analysis of ITS sequences, in identifying the isolates to species level, and that IRAP and REMAP markers can be used for studying the genetic variability in the genus Diaporthe particularly at the intraspecific level. The combined use of molecular tools such as multilocus phylogenetic approach and molecular markers, as performed in this study, is the best way to distinguish endophytic strains of Diaporthe isolated from common bean (Phaseolus vulgaris L.). © 2015 The Society for Applied Microbiology.

  13. The common sense model of self-regulation and psychological adjustment to predictive genetic testing: a prospective study.

    Science.gov (United States)

    van Oostrom, Iris; Meijers-Heijboer, Hanne; Duivenvoorden, Hugo J; Bröcker-Vriends, Annette H J T; van Asperen, Christi J; Sijmons, Rolf H; Seynaeve, Caroline; Van Gool, Arthur R; Klijn, Jan G M; Tibben, Aad

    2007-12-01

    This prospective study explored the contribution of illness representations and coping to cancer-related distress in unaffected individuals undergoing predictive genetic testing for an identified mutation in BRCA1/2 (BReast CAncer) or an HNPCC (Hereditary Nonpolyposis Colorectal Cancer)-related gene, based on the common sense model of self-regulation. Coping with hereditary cancer (UCL), illness representations (IPQ-R) and risk perception were assessed in 235 unaffected applicants for genetic testing before test result disclosure. Hereditary cancer distress (IES) and cancer worry (CWS) were assessed before, 2 weeks after and 6 months after result disclosure. Timeline (r = 0.30), consequences (r = 0.25), illness coherence (r = 0.21) and risk perception (r = 0.20) were significantly correlated to passive coping. Passive coping predicted hereditary cancer distress and cancer worry from pre-test (beta = 0.46 and 0.42, respectively) up to 6 months after result disclosure (beta = 0.32 and 0.19, respectively). Illness coherence predicted hereditary cancer distress up to 6 months after result disclosure (beta = 0.24), too. The self-regulatory model may be useful to predict the cognitive and emotional reactions to genetic cancer susceptibility testing. Identifying unhelpful representations and cognitive restructuring may be appropriate interventions to help distressed individuals undergoing genetic susceptibility testing for a BRCA1/2 or a HNPCC-related mutation.

  14. Genetic Algorithm Optimizes Q-LAW Control Parameters

    Science.gov (United States)

    Lee, Seungwon; von Allmen, Paul; Petropoulos, Anastassios; Terrile, Richard

    2008-01-01

    A document discusses a multi-objective, genetic algorithm designed to optimize Lyapunov feedback control law (Q-law) parameters in order to efficiently find Pareto-optimal solutions for low-thrust trajectories for electronic propulsion systems. These would be propellant-optimal solutions for a given flight time, or flight time optimal solutions for a given propellant requirement. The approximate solutions are used as good initial solutions for high-fidelity optimization tools. When the good initial solutions are used, the high-fidelity optimization tools quickly converge to a locally optimal solution near the initial solution. Q-law control parameters are represented as real-valued genes in the genetic algorithm. The performances of the Q-law control parameters are evaluated in the multi-objective space (flight time vs. propellant mass) and sorted by the non-dominated sorting method that assigns a better fitness value to the solutions that are dominated by a fewer number of other solutions. With the ranking result, the genetic algorithm encourages the solutions with higher fitness values to participate in the reproduction process, improving the solutions in the evolution process. The population of solutions converges to the Pareto front that is permitted within the Q-law control parameter space.

  15. Genetic map of the common bean using a breeding population derived from the Mesoamerican gene pool

    Directory of Open Access Journals (Sweden)

    Luciana Gomes Ferreira

    2010-01-01

    Full Text Available The mapping population consisted of 94 F2 generation plants derived from a cross between the CNFC 7812and CNFC 8056 lines, with different protein contents, 24% and 19% respectively. Seven hundred and fifty-two molecularmarkers were tested among the parents and four individuals from the segregant population. A total of 101 loci were used todevelop the genetic map. The polymorphism rate was 8.3% and 23.2% for the microsatellite and RAPD markers, respectively.The sizes of the linkage groups ranged from 6.7 to 139.0 cM , presenting a mean of 49.4 ± 36.8. The map length was 840.7cM and the mean group length was 45.9 cM. The average distance between the framework loci was 16.1 cM. This map wascompared with international reference bean maps and results were discussed. The construction of the genetic map fromparents of the same center of origin and the commercial grain type were discussed.

  16. Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis

    Science.gov (United States)

    Sieberts, Solveig K.; Zhu, Fan; García-García, Javier; Stahl, Eli; Pratap, Abhishek; Pandey, Gaurav; Pappas, Dimitrios; Aguilar, Daniel; Anton, Bernat; Bonet, Jaume; Eksi, Ridvan; Fornés, Oriol; Guney, Emre; Li, Hongdong; Marín, Manuel Alejandro; Panwar, Bharat; Planas-Iglesias, Joan; Poglayen, Daniel; Cui, Jing; Falcao, Andre O.; Suver, Christine; Hoff, Bruce; Balagurusamy, Venkat S. K.; Dillenberger, Donna; Neto, Elias Chaibub; Norman, Thea; Aittokallio, Tero; Ammad-ud-din, Muhammad; Azencott, Chloe-Agathe; Bellón, Víctor; Boeva, Valentina; Bunte, Kerstin; Chheda, Himanshu; Cheng, Lu; Corander, Jukka; Dumontier, Michel; Goldenberg, Anna; Gopalacharyulu, Peddinti; Hajiloo, Mohsen; Hidru, Daniel; Jaiswal, Alok; Kaski, Samuel; Khalfaoui, Beyrem; Khan, Suleiman Ali; Kramer, Eric R.; Marttinen, Pekka; Mezlini, Aziz M.; Molparia, Bhuvan; Pirinen, Matti; Saarela, Janna; Samwald, Matthias; Stoven, Véronique; Tang, Hao; Tang, Jing; Torkamani, Ali; Vert, Jean-Phillipe; Wang, Bo; Wang, Tao; Wennerberg, Krister; Wineinger, Nathan E.; Xiao, Guanghua; Xie, Yang; Yeung, Rae; Zhan, Xiaowei; Zhao, Cheng; Calaza, Manuel; Elmarakeby, Haitham; Heath, Lenwood S.; Long, Quan; Moore, Jonathan D.; Opiyo, Stephen Obol; Savage, Richard S.; Zhu, Jun; Greenberg, Jeff; Kremer, Joel; Michaud, Kaleb; Barton, Anne; Coenen, Marieke; Mariette, Xavier; Miceli, Corinne; Shadick, Nancy; Weinblatt, Michael; de Vries, Niek; Tak, Paul P.; Gerlag, Danielle; Huizinga, Tom W. J.; Kurreeman, Fina; Allaart, Cornelia F.; Louis Bridges Jr., S.; Criswell, Lindsey; Moreland, Larry; Klareskog, Lars; Saevarsdottir, Saedis; Padyukov, Leonid; Gregersen, Peter K.; Friend, Stephen; Plenge, Robert; Stolovitzky, Gustavo; Oliva, Baldo; Guan, Yuanfang; Mangravite, Lara M.

    2016-01-01

    Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h2=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data. PMID:27549343

  17. Evaluating the contribution of genetics and familial shared environment to common disease using the UK Biobank.

    Science.gov (United States)

    Muñoz, María; Pong-Wong, Ricardo; Canela-Xandri, Oriol; Rawlik, Konrad; Haley, Chris S; Tenesa, Albert

    2016-09-01

    Genome-wide association studies have detected many loci underlying susceptibility to disease, but most of the genetic factors that contribute to disease susceptibility remain unknown. Here we provide evidence that part of the 'missing heritability' can be explained by an overestimation of heritability. We estimated the heritability of 12 complex human diseases using family history of disease in 1,555,906 individuals of white ancestry from the UK Biobank. Estimates using simple family-based statistical models were inflated on average by ∼47% when compared with those from structural equation modeling (SEM), which specifically accounted for shared familial environmental factors. In addition, heritabilities estimated using SNP data explained an average of 44.2% of the simple family-based estimates across diseases and an average of 57.3% of the SEM-estimated heritabilities, accounting for almost all of the SEM heritability for hypertension. Our results show that both genetics and familial environment make substantial contributions to familial clustering of disease.

  18. Cryptic distant relatives are common in both isolated and cosmopolitan genetic samples.

    Directory of Open Access Journals (Sweden)

    Brenna M Henn

    Full Text Available Although a few hundred single nucleotide polymorphisms (SNPs suffice to infer close familial relationships, high density genome-wide SNP data make possible the inference of more distant relationships such as 2(nd to 9(th cousinships. In order to characterize the relationship between genetic similarity and degree of kinship given a timeframe of 100-300 years, we analyzed the sharing of DNA inferred to be identical by descent (IBD in a subset of individuals from the 23andMe customer database (n = 22,757 and from the Human Genome Diversity Panel (HGDP-CEPH, n = 952. With data from 121 populations, we show that the average amount of DNA shared IBD in most ethnolinguistically-defined populations, for example Native American groups, Finns and Ashkenazi Jews, differs from continentally-defined populations by several orders of magnitude. Via extensive pedigree-based simulations, we determined bounds for predicted degrees of relationship given the amount of genomic IBD sharing in both endogamous and 'unrelated' population samples. Using these bounds as a guide, we detected tens of thousands of 2(nd to 9(th degree cousin pairs within a heterogenous set of 5,000 Europeans. The ubiquity of distant relatives, detected via IBD segments, in both ethnolinguistic populations and in large 'unrelated' populations samples has important implications for genetic genealogy, forensics and genotype/phenotype mapping studies.

  19. Genetic divergence in the common bean (Phaseolus vulgaris L.) in the Cerrado-Pantanal ecotone.

    Science.gov (United States)

    da Silva, F A; Corrêa, A M; Teodoro, P E; Lopes, K V; Corrêa, C C G

    2017-03-30

    Evaluating genetic diversity among genotypes is important for providing parameters for the identification of superior genotypes, because the choice of parents that form segregating populations is crucial. Our objectives were to i) evaluate agronomic performance; ii) compare clustering methods; iii) ascertain the relative contributions of the variables evaluated; and iv) identify the most promising hybrids to produce superior segregating populations. The trial was conducted in 2015 at the State University of Mato Grosso do Sul, Brazil. We used a randomized block design with three replications, and recorded the days to emergence, days to flowering, days to maturity, plant height, number of branches, number of pods, number of seeds per pod, weight of 100 grains, and productivity. The genetic diversity of the genotypes was determined by cluster analysis using two dissimilarity measures: the Euclidean distance and the standardized mean Mahalanobis distance using the Ward hierarchical method. The genotypes 'CNFC 10762', 'IAC Dawn', and 'BRS Style' had the highest grain yields, and clusters that were based on the Euclidean distance differed from those based on the Mahalanobis distance, the second being more precise. The yield grain character has greater relevance to the dispute. Hybrids with a high heterotic effect can be obtained by crossing 'IAC Alvorada' with 'CNFC 10762', 'IAC Alvorada' with 'CNFC 10764', and 'BRS Style' with 'IAC Alvorada'.

  20. Genetic diversity, inter-gene pool introgression and nutritional quality of common beans (Phaseolus vulgaris L.) from Central Africa.

    Science.gov (United States)

    Blair, Matthew W; González, Laura F; Kimani, Paul M; Butare, Louis

    2010-07-01

    The Great Lakes region of Central Africa is a major producer of common beans in Africa. The region is known for high population density and small average farm size. The common bean represents the most important legume crop of the region, grown on over a third of the cultivated land area, and the per capita consumption is among the highest in the world for the food crop. The objective of this study was to evaluate the genetic diversity in a collection of 365 genotypes from the Great Lakes region of Central Africa, including a large group of landraces from Rwanda as well as varieties from primary centers of diversity and from neighboring countries of Central Africa, such as the Democratic Republic of Congo and Uganda, using 30 fluorescently labeled microsatellite markers and automated allele detection. In addition, the landraces were evaluated for their seed iron and zinc concentration to determine if genetic diversity influenced nutritional quality. Principal coordinate and neighbor-joining analyses allowed the separation of the landraces into 132 Andean and 195 Mesoamerican (or Middle American) genotypes with 32 landraces and 6 varieties intermediate between the gene pools and representing inter-gene pool introgression in terms of seed characteristics and alleles. Genetic diversity and the number of alleles were high for the collection, reflecting the preference for a wide range of seed types in the region and no strong commercial class preference, although red, red mottled and brown seeded beans were common. Observed heterozygosity was also high and may be explained by the common practice of maintaining seed and plant mixtures, a coping strategy practiced by Central African farmers to reduce the effects of abiotic and biotic stresses. Finally, nutritional quality differed between the gene pools with respect to seed iron and zinc concentration, while genotypes from the intermediate group were notably high in both minerals. In conclusion, this study has shown that

  1. Genetic screens to identify pathogenic gene variants in the common cancer predisposition Lynch syndrome

    DEFF Research Database (Denmark)

    Drost, Mark; Lützen, Anne; van Hees, Sandrine

    2013-01-01

    In many individuals suspected of the common cancer predisposition Lynch syndrome, variants of unclear significance (VUS), rather than an obviously pathogenic mutations, are identified in one of the DNA mismatch repair (MMR) genes. The uncertainty of whether such VUS inactivate MMR, and therefore...... for the translation of personalized genomics into targeted healthcare....

  2. What causes myopia? : Complex genetics and epidemiology of a common condition

    NARCIS (Netherlands)

    V.J.M. Verhoeven (Virginie)

    2015-01-01

    markdownabstract__Abstract__ Myopia (nearsightedness) is a highly common eye condition that is predominantly caused by an axial elongation of the eye. Myopia can usually be corrected with negative glasses, contact lenses, and/or laser refractive surgery. Unfortunately, however, high myopia (-6 diop

  3. Genetics and mapping of a new anthracnose resistance Locus in Andean common bean Paloma

    Science.gov (United States)

    The Andean cultivar Paloma is resistant to Mesoamerican and Andean races of Colletotrichum lindemuthianum, the fungal pathogen that causes the destructive anthracnose disease of common bean. Remarkably, Paloma is resistant to Mesoamerican races 2047 and 3481, which are among the most virulent races ...

  4. Genome-wide genetic dissection of supernumerary spikelet and related traits in common wheat

    Science.gov (United States)

    Branched spike or supernumerary spikelet (SS) is a naturally occurring variant in wheat and holds great potential for increasing the number of grains per spike, and ultimately, increasing wheat yield. However, detailed knowledge of the molecular basis of spike branching in common wheat is lacking. I...

  5. Search for Common Molecular Genetic Markers of Nosocomial Pneumonia and Acute Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    T. V. Smelaya

    2015-01-01

    Full Text Available Genetic predisposition partially accounts for the clinical variability of the course of an infectious process. A total of 750 people, including 419 (81.1% male patients aged 42.9±0.9 years, admitted to the clinics of the V. A. Negovsky Research Institute of General Reanimatology (Moscow, Russia, were genotyped to establish the influence of genetic factors on their susceptibility to critical conditions.Materials and methods. Tetra-primer allele-specific polymerase chain reaction was used to investigate single-nucleotide polymorphisms (SNP in the xenobiotic detoxification and oxidative stress genes (CYP1A1 (three sites, AhR, ABCB1, SOD2, GCLC and CAT and in the vascular homeostasis genes (ACE, AGT, AGTR1, NOS3, VEGFα and MTHFR.Results. A total of 268 nosocomial pneumonia (NP cases were registered in a patient group. Individual SNP analysis has shown that among the patients with NP the risk of acute respiratory distress syndrome (ARDS is associated with the carriage of the following genotypes: CYP1A1 rs2606345-Т/Т (p=0.0027, OR=2.38; 95% CI: 1.35—4.17 and AhRrs2066853-G/A-A/A (p=0.0012, OR=2.94; 95% CI: 1.54—5.60. The frequency of the C allele of the AGTR1 gene (re5186 was much higher among the survivors (in the NP group. The assessment of a multiplicative genetic model of genes that had demonstrated the highest single-locus effects because of a ARDS risk, as well as in-hospital mortality, could establish the complex genotype including a combination of risky alleles of the detoxi- fication and vascular homeostasis genes (CYP1A1 rs2606345-T — AhR rs2066853-A and ACE rs4340-D — AGT rs699-C — AGTR1 rs5186-C, which was associated with the increased risk of both NP and ARDS, as well as with the likelihood of a fatal outcome.Conclusion. An understanding of the risk factors of NP and ARDS will aid in predicting the outcome of the underlying disease and in developing possible preventive measures. 

  6. Genetic analysis of QTL for eye cross and eye diameter in common carp (Cyprinus carpio L.) using microsatellites and SNPs.

    Science.gov (United States)

    Jin, S B; Zhang, X F; Lu, J G; Fu, H T; Jia, Z Y; Sun, X W

    2015-04-17

    A group of 107 F1 hybrid common carp was used to construct a linkage map using JoinMap 4.0. A total of 4877 microsatellite and single nucleotide polymorphism (SNP) markers isolated from a genomic library (978 microsatellite and 3899 SNP markers) were assigned to construct the genetic map, which comprised 50 linkage groups. The total length of the linkage map for the common carp was 4775.90 cM with an average distance between markers of 0.98 cM. Ten quantitative trait loci (QTL) were associated with eye diameter, corresponding to 10.5-57.2% of the total phenotypic variation. Twenty QTL were related to eye cross, contributing to 10.8-36.9% of the total phenotypic variation. Two QTL for eye diameter and four QTL for eye cross each accounted for more than 20% of the total phenotypic variation and were considered to be major QTL. One growth factor related to eye diameter was observed on LG10 of the common carp genome, and three growth factors related to eye cross were observed on LG10, LG35, and LG44 of the common carp genome. The significant positive relationship of eye cross and eye diameter with other commercial traits suggests that eye diameter and eye cross can be used to assist in indirect selection for many commercial traits, particularly body weight. Thus, the growth factor for eye cross may also contribute to the growth of body weight, implying that aggregate breeding could have multiple effects. These findings provide information for future genetic studies and breeding of common carp.

  7. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

    DEFF Research Database (Denmark)

    Jim, Heather S L; Lin, Hui-Yi; Tyrer, Jonathan P;

    2016-01-01

    ,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant...

  8. Evolutionary biology and genetic techniques for insect control

    OpenAIRE

    Leftwich, Philip; Bolton, Michael; Chapman, Tracey

    2015-01-01

    Abstract The requirement to develop new techniques for insect control that minimize negative environmental impacts has never been more pressing. Here we discuss population suppression and population replacement technologies. These include sterile insect technique, genetic elimination methods such as the release of insects carrying a dominant lethal (RIDL), and gene driving mechanisms offered by intracellular bacteria and homing endonucleases. We also review the potential of newer or underutil...

  9. Evidence for mitochondrial genetic control of autosomal gene expression.

    Science.gov (United States)

    Kassam, Irfahan; Qi, Tuan; Lloyd-Jones, Luke; Holloway, Alexander; Jan Bonder, Marc; Henders, Anjali K; Martin, Nicholas G; Powell, Joseph E; Franke, Lude; Montgomery, Grant W; Visscher, Peter M; McRae, Allan F

    2016-10-18

    The mitochondrial and nuclear genomes coordinate and co-evolve in eukaryotes in order to adapt to environmental changes. Variation in the mitochondrial genome is capable of affecting expression of genes on the nuclear genome. Sex-specific mitochondrial genetic control of gene expression has been demonstrated in Drosophila melanogaster, where males were found to drive most of the total variation in gene expression. This has potential implications for male-related health and disease resulting from variation in mtDNA solely inherited from the mother. We used a family-based study comprised of 47,323 gene expression probes and 78 mitochondrial SNPs (mtSNPs) from n = 846 individuals to examine the extent of mitochondrial genetic control of gene expression in humans. This identified 15 significant probe-mtSNP associations (P[Formula: see text]) corresponding to 5 unique genes on the mitochondrial and nuclear genomes, with three of these genes corresponding to mitochondrial genetic control of gene expression in the nuclear genome. The associated mtSNPs for three genes (one cis and two trans associations) were replicated (P expression in any of these five probes. Sex-specific effects were examined by applying our analysis to males and females separately and testing for differences in effect size. The MEST gene was identified as having the most significantly different effect sizes across the sexes (P [Formula: see text]). MEST was similarly expressed in males and females with the G allele; however, males with the C allele are highly expressed for MEST, while females show no expression of the gene. This study provides evidence for the mitochondrial genetic control of expression of several genes in humans, with little evidence found for sex-specific effects.

  10. Direct detection of common and rare inversion mutations in the genetic diagnosis of severe hemophilia A

    Energy Technology Data Exchange (ETDEWEB)

    Windsor, A.S.; Lillicrap, D.P.; Taylor, S.A.M. [Queen`s Univ., Ontario (Canada)

    1994-09-01

    Approximately 50% of the cases of severe hemophilia A (factor VIII:C < 0.01 units/ml) may be due to gross rearrangements of the factor VIII gene. The mutation involves homologous sequences upstream of the factor VIII locus and within intron 22 in an intrachromosomal recombination, inversion, event. The rearrangements can readily be detected on a Southern blot using a probe that is complementary to sequences from within intron 22. We describe here the analysis of this mutation in 71 severe hemophilia A patients. Thirty two of the patients (45%) showed evidence of a rearrangement. Five different patterns of rearrangements were seen, two of which have previously been described and account for the majority of cases (pattern 1, 70% and pattern 2, 16%). Three other abnormal patterns were observed. The inversion mechanism does not usually result in the loss or gain of any genetic material, but in one patient, in whom a unique rearrangement pattern was observed (pattern 3), we have previously documented a gross deletion which removes exons 1-22 of the factor VII gene as well as sequences 5{prime} to the gene. In another individual a fourth pattern in which an extra 19.0 kb band is present was detected. In this case it is unclear as to whether the rearrangement is responsible for the disease or is simply coincident normal variation. A fifth pattern, in which an extra 16.0 kb band was detected, was observed in a family with a new mutation causing hemophilia A. The affected individual and his mother inherited a de novo rearrangement of the factor VIII gene from his unaffected grandfather, implicating it as the cause of the disease. In conclusion, testing for the factor VIII inversion mutation was positive in approximately 45% of severe hemophiliacs, 72% of whom were isolated cases, and as such should constitute the initial stage in the genetic testing protocol for these patients` families.

  11. Common genetic polymorphisms within NFκB-related genes and the risk of developing invasive aspergillosis

    Directory of Open Access Journals (Sweden)

    Carmen Belén Lupiañez

    2016-08-01

    Full Text Available Invasive Aspergillosis (IA is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mould. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NFκB1, NFκB2, RelA, RelB, Rel and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non-IA recruited through a collaborative effort involving the aspBIOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT-stratified analysis revealed that carriers of the IRF4rs12203592T/T genotype had a 6-fold increased risk of developing the infection when compared with those carrying the C allele (OR-Rec=6.24, 95%CI 1.25-31.2, P=0.026, the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4AATC and IRF4GGTC haplotypes (not including the IRF4rs12203592T risk allele with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4rs12203592 SNP. Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA.

  12. Genetic variation, phenotypic stability, and repeatability of drought response in European larch throughout 50 years in a common garden experiment.

    Science.gov (United States)

    George, Jan-Peter; Grabner, Michael; Karanitsch-Ackerl, Sandra; Mayer, Konrad; Weißenbacher, Lambert; Schueler, Silvio; Mäkelä, Annikki

    2017-01-31

    Assessing intra-specific variation in drought stress response is required to mitigate the consequences of climate change on forest ecosystems. Previous studies suggest that European larch (Larix decidua Mill.), an important European conifer in mountainous and alpine forests, is highly vulnerable to drought. In light of this, we estimated the genetic variation in drought sensitivity and its degree of genetic determination in a 50-year-old common garden experiment in the drought-prone northeastern Austria. Tree ring data from larch provenances originating from across the species' natural range were used to estimate the drought reaction in four consecutive drought events (1977, 1981, 1990–1994, and 2003) with extremely low standardized precipitation- and evapotranspiration-index values that affected growth in all provenances. We found significant differences among provenances across the four drought periods for the trees’ capacity to withstand drought (resistance) and for their capacity to reach pre-drought growth levels after drought (resilience). Provenances from the species' northern distribution limit in the Polish lowlands were found to be more drought resistant and showed higher stability across all drought periods than provenances from mountainous habitats at the southern fringe. The degree of genetic determination, as estimated by the repeatability, ranged up to 0.39, but significantly differed among provenances, indicating varying degrees of natural selection at the provenance origin. Generally, the relationship between the provenances’ source climate and drought behavior was weak, suggesting that the contrasting patterns of drought response are a result of both genetic divergence out of different refugial lineages and local adaptation to summer or winter drought conditions. Our analysis suggests that European larch posseses high genetic variation among and within provenances that can be used for assisted migration and breeding programs.

  13. ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties

    DEFF Research Database (Denmark)

    St Pourcain, B; Robinson, E B; Anttila, V

    2017-01-01

    Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic......-developing youth (Avon Longitudinal Study of Parents and Children, N⩽5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34...... effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social...

  14. Application of genetic algorithms to tuning fuzzy control systems

    Science.gov (United States)

    Espy, Todd; Vombrack, Endre; Aldridge, Jack

    1993-01-01

    Real number genetic algorithms (GA) were applied for tuning fuzzy membership functions of three controller applications. The first application is our 'Fuzzy Pong' demonstration, a controller that controls a very responsive system. The performance of the automatically tuned membership functions exceeded that of manually tuned membership functions both when the algorithm started with randomly generated functions and with the best manually-tuned functions. The second GA tunes input membership functions to achieve a specified control surface. The third application is a practical one, a motor controller for a printed circuit manufacturing system. The GA alters the positions and overlaps of the membership functions to accomplish the tuning. The applications, the real number GA approach, the fitness function and population parameters, and the performance improvements achieved are discussed. Directions for further research in tuning input and output membership functions and in tuning fuzzy rules are described.

  15. 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...

  16. Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design.

    Science.gov (United States)

    Castaño-Vinyals, Gemma; Aragonés, Nuria; Pérez-Gómez, Beatriz; Martín, Vicente; Llorca, Javier; Moreno, Victor; Altzibar, Jone M; Ardanaz, Eva; de Sanjosé, Sílvia; Jiménez-Moleón, José Juan; Tardón, Adonina; Alguacil, Juan; Peiró, Rosana; Marcos-Gragera, Rafael; Navarro, Carmen; Pollán, Marina; Kogevinas, Manolis

    2015-01-01

    We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  17. Independent genetic control of maize (Zea mays L.) kernel weight determination and its phenotypic plasticity.

    Science.gov (United States)

    Alvarez Prado, Santiago; Sadras, Víctor O; Borrás, Lucas

    2014-08-01

    Maize kernel weight (KW) is associated with the duration of the grain-filling period (GFD) and the rate of kernel biomass accumulation (KGR). It is also related to the dynamics of water and hence is physiologically linked to the maximum kernel water content (MWC), kernel desiccation rate (KDR), and moisture concentration at physiological maturity (MCPM). This work proposed that principles of phenotypic plasticity can help to consolidated the understanding of the environmental modulation and genetic control of these traits. For that purpose, a maize population of 245 recombinant inbred lines (RILs) was grown under different environmental conditions. Trait plasticity was calculated as the ratio of the variance of each RIL to the overall phenotypic variance of the population of RILs. This work found a hierarchy of plasticities: KDR ≈ GFD > MCPM > KGR > KW > MWC. There was no phenotypic and genetic correlation between traits per se and trait plasticities. MWC, the trait with the lowest plasticity, was the exception because common quantitative trait loci were found for the trait and its plasticity. Independent genetic control of a trait per se and genetic control of its plasticity is a condition for the independent evolution of traits and their plasticities. This allows breeders potentially to select for high or low plasticity in combination with high or low values of economically relevant traits.

  18. Genetic control of astrocyte function in neural circuits

    Directory of Open Access Journals (Sweden)

    Hannah Maria Jahn

    2015-08-01

    Full Text Available During the last two decades numerous genetic approaches affecting cell function in vivo have been developed. Current state-of-the-art technology permits the selective switching of gene function in distinct cell populations within the complex organization of a given tissue parenchyma. The tamoxifen-inducible Cre/loxP gene recombination and the doxycycline-dependent modulation of gene expression are probably the most popular genetic paradigms.Here, we will review applications of these two strategies while focussing on the interactions of astrocytes and neurons in the central nervous system (CNS and their impact for the whole organism. Abolishing glial sensing of neuronal activity by selective deletion of glial transmitter receptors demonstrated the impact of astrocytes for higher cognitive functions such as learning and memory, or the more basic body control of muscle coordination. Interestingly, also interfering with glial output, i.e. the release of gliotransmitters can drastically change animal’s physiology like sleeping behavior. Furthermore, such genetic approaches have also been used to restore astrocyte function. In these studies two alternatives were employed to achieve proper genetic targeting of astrocytes: transgenes using the promoter of the human glial fibrillary acidic protein (GFAP or homologous recombination into the glutamate-aspartate transporter (GLAST locus. We will highlight their specific properties that could be relevant for their use.

  19. Cofactor of BRCA1: A new genetic marker for common malignant liver cancer

    Directory of Open Access Journals (Sweden)

    Editorial Office

    2016-08-01

    Full Text Available A new study has identified a vital gene in the pathogenesis and progression of liver cancer hepatocellular carcinoma (HCC, according to a team of biotechnology researchers at The American University in Cairo, Egypt, in a scientific paper published recently by AMOR. The study on human gene ‘Cofactor of BRCA1’ (dubbed COBRA1 and its potential role as a reliable cancer predictor for HCC is especially important due to the disease’s grim outlook. HCC is “ranked as the second most common cause of cancer-related deaths in the world in 2012,” the authors said. “Thus, it is considered as a highly aggressive cancer with poor prognosis,” they added. According to data from the Surveillance Epidemiology and End Results (SEER program, hepatocellular carcinoma accounts for 90% of all liver cancers worldwide. In the United States, HCC represents the fastest growing cause of cancer mortality overall and the second fastest growing cause of cancer deaths among women. Globally, the incidence of HCC in developing nations is over twice that of in developed countries – East Asia having highest incidence of HCC with the rate of 35 male cases per 100,000, followed by the continent of Africa. HCC mortality statistics in the developing countries is also more than double compared to the First World nations, with the annual loss of 33.5 and 23.73 lives per 100,000 in Asia and Africa, respectively. In addition, “HCC is usually diagnosed in the late stages of the tumor where, at some point, treatment is of limited efficacy. Thus, prognoses and follow-ups are necessary to regularly assess the patients and to predict any risks before the deterioration of patients’ condition,” said researcher Aya Youssef and her fellow team members. The behaviour of COBRA1 in the development and progression of several cancers has previously been studied and established, the researchers wrote. “For example, cell lines and tissues isolated from late-stage metastatic breast

  20. Common Genetic Variant in VIT Is Associated with Human Brain Asymmetry.

    Science.gov (United States)

    Tadayon, Sayed H; Vaziri-Pashkam, Maryam; Kahali, Pegah; Ansari Dezfouli, Mitra; Abbassian, Abdolhossein

    2016-01-01

    Brain asymmetry varies across individuals. However, genetic factors contributing to this normal variation are largely unknown. Here we studied variation of cortical surface area asymmetry in a large sample of subjects. We performed principal component analysis (PCA) to capture correlated asymmetry variation across cortical regions. We found that caudal and rostral anterior cingulate together account for a substantial part of asymmetry variation among individuals. To find SNPs associated with this subset of brain asymmetry variation we performed a genome-wide association study followed by replication in an independent cohort. We identified one SNP (rs11691187) that had genome-wide significant association (P Combined = 2.40e-08). The rs11691187 is in the first intron of VIT. In a follow-up analysis, we found that VIT gene expression is associated with brain asymmetry in six donors of the Allen Human Brain Atlas. Based on these findings we suggest that VIT contributes to normal brain asymmetry variation. Our results can shed light on disorders associated with altered brain asymmetry.

  1. [Genetic diversity of rhizobia isolated from common legumes in the Karst area. Northwest Guangxi].

    Science.gov (United States)

    Liu, Lu; He, Xun-yang; Xie, Qiang; Wang, Ke-lin

    2015-12-01

    Legumes, with a strong resistance to the adverse environmental conditions, are pioneer plants in degraded habitats, and play an important role in ecosystem restoration. In this study, the nodulation characteristics of 24 legumes were surveyed in the Karst area of Northwest Guangxi. A total of 39 nodule samples were collected from 15 legumes, the DNA was extracted and the 16S rDNA and nifH gene were amplified. A phylogenetic tree was then constructed to analyze the genetic diversity of rhizobia. The results showed that 15 legumes were nodulated, of which 14 belonged to the Papilionoideae, one to the Mimosaceae, and none to the Caesalpinoideae. No nodules were found on some legumes that were reported as nodulated, which might result from soil water stress in Karst. BLAST result and phylogenetic analyse indicated that most of the legumes were associated with rhizobia that belonged to the genus Bradyrhizobium, with the exception of two samples from Callerya nitida that were associated with the genus Mesorhizobium. In the phylogenetic tree, the sequences obtained from the same plot or the sequences from the same host species clustered together in most cases. This finding suggested that host selection and the ecological environment are the major factors that influence the genotype of rhizobia.

  2. 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.

  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.; 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

  4. Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.

    Directory of Open Access Journals (Sweden)

    Guangju Zhai

    2011-04-01

    Full Text Available Dehydroepiandrosterone sulphate (DHEAS is the most abundant circulating steroid secreted by adrenal glands--yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15 × 10(-36, SULT2A1 (rs2637125; p =  2.61 × 10(-19, ARPC1A (rs740160; p =  1.56 × 10(-16, TRIM4 (rs17277546; p =  4.50 × 10(-11, BMF (rs7181230; p = 5.44 × 10(-11, HHEX (rs2497306; p =  4.64 × 10(-9, BCL2L11 (rs6738028; p = 1.72 × 10(-8, and CYP2C9 (rs2185570; p = 2.29 × 10(-8. These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS.

  5. Implications of early selection for resistance to anthracnose in genetic breeding of common bean

    Directory of Open Access Journals (Sweden)

    José Maria Villela Pádua

    2015-08-01

    Full Text Available It is questionable if early selection for resistance to Colletotrichum lindemuthianum reduces the efficiency of selection for grain yield in common beans. For this, it was used the segregating population of the cross between two common bean lines: CI107 (susceptible x BRSMG Madrepérola (resistant. Selection for resistance was carried out in F2 and F3 , obtaining three types of progenies: not selected (A, selected only in F2 (B, and selected in F2 andF3 (C. The progenies obtained were evaluated for grain yield and pathogen occurrence in experiments. In F3:5, it was used 289 treatments (96 progenies A, 96 B, 95 C and 2 checks (T; in F3:6, 196 treatments (64 A, 64 B, 64 C and 4 T; in F3:7, 81 treatments (26 A, 26 B, 26 C and 3 T. Selection of plants resistant to anthracnose in early generations increases the successful selection for grain yield in later generations.

  6. Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.

    Directory of Open Access Journals (Sweden)

    Guangju Zhai

    2011-04-01

    Full Text Available Dehydroepiandrosterone sulphate (DHEAS is the most abundant circulating steroid secreted by adrenal glands--yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15 × 10(-36, SULT2A1 (rs2637125; p =  2.61 × 10(-19, ARPC1A (rs740160; p =  1.56 × 10(-16, TRIM4 (rs17277546; p =  4.50 × 10(-11, BMF (rs7181230; p = 5.44 × 10(-11, HHEX (rs2497306; p =  4.64 × 10(-9, BCL2L11 (rs6738028; p = 1.72 × 10(-8, and CYP2C9 (rs2185570; p = 2.29 × 10(-8. These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS.

  7. Maine Coon renal screening: ultrasonographical characterisation and preliminary genetic analysis for common genes in cats with renal cysts.

    Science.gov (United States)

    Gendron, Karine; Owczarek-Lipska, Marta; Lang, Johann; Leeb, Tosso

    2013-12-01

    The objective of this study was to assess the prevalence of renal cysts and other renal abnormalities in purebred Maine Coon cats, and to characterise these through genetic typing. Voluntary pre-breeding screening programmes for polycystic kidney disease (PKD) are offered for this breed throughout Switzerland, Germany and other northern European countries. We performed a retrospective evaluation of Maine Coon screening for renal disease at one institution over an 8-year period. Renal ultrasonography was performed in 187 healthy Maine Coon cats. Renal changes were observed in 27 of these cats. Renal cysts were found in seven cats, and were mostly single and unilateral (6/7, 85.7%), small (mean 3.6 mm) and located at the corticomedullary junction (4/6, 66.7%). Sonographical changes indicating chronic kidney disease (CKD) were observed in 10/187 (5.3%) cats and changes of unknown significance were documented in 11/187 (5.9%) cats. All six cats genetically tested for PKD1 were negative for the mutation, and gene sequencing of these cats did not demonstrate any common genetic sequences. Cystic renal disease occurs with a low prevalence in Maine Coons and is unrelated to the PKD observed in Persians and related breeds. Ultrasonographical findings compatible with CKD are not uncommon in juvenile Maine Coons.

  8. Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans.

    Science.gov (United States)

    Bakken, Trygve E; Roddey, J Cooper; Djurovic, Srdjan; Akshoomoff, Natacha; Amaral, David G; Bloss, Cinnamon S; Casey, B J; Chang, Linda; Ernst, Thomas M; Gruen, Jeffrey R; Jernigan, Terry L; Kaufmann, Walter E; Kenet, Tal; Kennedy, David N; Kuperman, Joshua M; Murray, Sarah S; Sowell, Elizabeth R; Rimol, Lars M; Mattingsdal, Morten; Melle, Ingrid; Agartz, Ingrid; Andreassen, Ole A; Schork, Nicholas J; Dale, Anders M; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R; Jagust, William; Trojanowki, John Q; Toga, Arthur W; Beckett, Laurel; Green, Robert C; Saykin, Andrew J; Morris, John; Liu, Enchi; Montine, Tom; Gamst, Anthony; Thomas, Ronald G; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Harvey, Danielle; Kornak, John; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Bandy, Dan; Koeppe, Robert A; Foster, Norm; Reiman, Eric M; Chen, Kewei; Mathis, Chet; Cairns, Nigel J; Taylor-Reinwald, Lisa; Trojanowki, J Q; Shaw, Les; Lee, Virginia M Y; Korecka, Magdalena; Crawford, Karen; Neu, Scott; Foroud, Tatiana M; Potkin, Steven; Shen, Li; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Dolen, Sara; Schneider, Lon S; Pawluczyk, Sonia; Spann, Bryan M; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L; Lord, Joanne L; Johnson, Kris; Doody, Rachelle S; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S; Bell, Karen L; Morris, John C; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Mitsis, Effie; Romirowsky, Aliza; deToledo-Morrell, Leyla; Shah, Raj C; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; Kielb, Stephanie; Rusinek, Henry; de Leon, Mony J; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P Murali; Petrella, Jeffrey R; Coleman, R Edward; Arnold, Steven E; Karlawish, Jason H; Wolk, David; Smith, Charles D; Jicha, Greg; Hardy, Peter; Lopez, Oscar L; Oakley, MaryAnn; Simpson, Donna M; Porsteinsson, Anton P; Goldstein, Bonnie S; Martin, Kim; Makino, Kelly M; Ismail, M Saleem; Brand, Connie; Mulnard, Ruth A; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I; Lah, James J; Cellar, Janet S; Burns, Jeffrey M; Anderson, Heather S; Swerdlow, Russell H; Apostolova, Liana; Lu, Po H; Bartzokis, George; Silverman, Daniel H S; Graff-Radford, Neill R; Parfitt, Francine; Johnson, Heather; Farlow, Martin R; Hake, Ann Marie; Matthews, Brandy R; Herring, Scott; van Dyck, Christopher H; Carson, Richard E; MacAvoy, Martha G; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Ging-Yuek; Hsiung, Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristina; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A; Johnson, Keith A; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan; Belden, Christine; Jacobson, Sandra; Kowall, Neil; Killiany, Ronald; Budson, Andrew E; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O; Wolday, Saba; Bwayo, Salome K; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; Fletcher, Evan; Carmichael, Owen; Olichney, John; Kittur, Smita; Borrie, Michael; Lee, T-Y; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M; Potkin, Steven G; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W; Kataki, Maria; Zimmerman, Earl A; Celmins, Dzintra; Brown, Alice D; Pearlson, Godfrey D; Blank, Karen; Anderson, Karen; Santulli, Robert B; Schwartz, Eben S; Sink, Kaycee M; Williamson, Jeff D; Garg, Pradeep; Watkins, Franklin; Ott, Brian R; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J; Miller, Bruce L; Mintzer, Jacobo; Longmire, Crystal Flynn; Spicer, Kenneth; Finger, Elizabether; Rachinsky, Irina; Drost, Dick; Jernigan, Terry; McCabe, Connor; Grant, Ellen; Ernst, Thomas; Kuperman, Josh; Chung, Yoon; Murray, Sarah; Bloss, Cinnamon; Darst, Burcu; Pritchett, Lexi; Saito, Ashley; Amaral, David; DiNino, Mishaela; Eyngorina, Bella; Sowell, Elizabeth; Houston, Suzanne; Soderberg, Lindsay; Kaufmann, Walter; van Zijl, Peter; Rizzo-Busack, Hilda; Javid, Mohsin; Mehta, Natasha; Ruberry, Erika; Powers, Alisa; Rosen, Bruce; Gebhard, Nitzah; Manigan, Holly; Frazier, Jean; Kennedy, David; Yakutis, Lauren; Hill, Michael; Gruen, Jeffrey; Bosson-Heenan, Joan; Carlson, Heatherly

    2012-03-06

    Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P(combined) = 3.2 × 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5' UTR of GPCPD1, glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.

  9. Optimal control strategy of malaria vector using genetically modified mosquitoes.

    Science.gov (United States)

    Rafikov, M; Bevilacqua, L; Wyse, A P P

    2009-06-07

    The development of transgenic mosquitoes that are resistant to diseases may provide a new and effective weapon of diseases control. Such an approach relies on transgenic mosquitoes being able to survive and compete with wild-type populations. These transgenic mosquitoes carry a specific code that inhibits the plasmodium evolution in its organism. It is said that this characteristic is hereditary and consequently the disease fades away after some time. Once transgenic mosquitoes are released, interactions between the two populations and inter-specific mating between the two types of mosquitoes take place. We present a mathematical model that considers the generation overlapping and variable environment factors. Based on this continuous model, the malaria vector control is formulated and solved as an optimal control problem, indicating how genetically modified mosquitoes should be introduced in the environment. Numerical simulations show the effectiveness of the proposed control.

  10. Genetic and Environmental Control of Neurodevelopmental Robustness in Drosophila.

    Directory of Open Access Journals (Sweden)

    David J Mellert

    Full Text Available Interindividual differences in neuronal wiring may contribute to behavioral individuality and affect susceptibility to neurological disorders. To investigate the causes and potential consequences of wiring variation in Drosophila melanogaster, we focused on a hemilineage of ventral nerve cord interneurons that exhibits morphological variability. We find that late-born subclasses of the 12A hemilineage are highly sensitive to genetic and environmental variation. Neurons in the second thoracic segment are particularly variable with regard to two developmental decisions, whereas its segmental homologs are more robust. This variability "hotspot" depends on Ultrabithorax expression in the 12A neurons, indicating variability is cell-intrinsic and under genetic control. 12A development is more variable and sensitive to temperature in long-established laboratory strains than in strains recently derived from the wild. Strains with a high frequency of one of the 12A variants also showed a high frequency of animals with delayed spontaneous flight initiation, whereas other wing-related behaviors did not show such a correlation and were thus not overtly affected by 12A variation. These results show that neurodevelopmental robustness is variable and under genetic control in Drosophila and suggest that the fly may serve as a model for identifying conserved gene pathways that stabilize wiring in stressful developmental environments. Moreover, some neuronal lineages are variation hotspots and thus may be more amenable to evolutionary change.

  11. Simple Algorithms to Calculate Asymptotic Null Distributions of Robust Tests in Case-Control Genetic Association Studies in R

    Directory of Open Access Journals (Sweden)

    Wing Kam Fung

    2010-02-01

    Full Text Available The case-control study is an important design for testing association between genetic markers and a disease. The Cochran-Armitage trend test (CATT is one of the most commonly used statistics for the analysis of case-control genetic association studies. The asymptotically optimal CATT can be used when the underlying genetic model (mode of inheritance is known. However, for most complex diseases, the underlying genetic models are unknown. Thus, tests robust to genetic model misspecification are preferable to the model-dependant CATT. Two robust tests, MAX3 and the genetic model selection (GMS, were recently proposed. Their asymptotic null distributions are often obtained by Monte-Carlo simulations, because they either have not been fully studied or involve multiple integrations. In this article, we study how components of each robust statistic are correlated, and find a linear dependence among the components. Using this new finding, we propose simple algorithms to calculate asymptotic null distributions for MAX3 and GMS, which greatly reduce the computing intensity. Furthermore, we have developed the R package Rassoc implementing the proposed algorithms to calculate the empirical and asymptotic p values for MAX3 and GMS as well as other commonly used tests in case-control association studies. For illustration, Rassoc is applied to the analysis of case-control data of 17 most significant SNPs reported in four genome-wide association studies.

  12. [Genetic background in common forms of obesity - from studies on identical twins to candidate genes of obesity].

    Science.gov (United States)

    Bendlová, Běla; Lukášová, Petra; Vaňková, Markéta; Vejražková, Daniela; Bradnová, Olga; Včelák, Josef; Stanická, Soňa; Zamrazilová, Hana; Aldhoon-Hainerová, Irena; Dušátková, Lenka; Kunešová, Marie; Hainer, Vojtěch

    2014-01-01

    Common obesity is a result of interaction between genes and environmental/lifestyle factors, with heritability estimates 40-70%. Not only the susceptibility to obesity but also the success of weight management depends on the genetic background of each individual. This paper summarizes the up-to-date knowledge on genetic causes of common obesities. Introduction of genome-wide association studies (GWAS) led to an identification of a total of 32 variants associated with obesity/BMI and 14 with body fat distribution. Further, a great progress in revealing the mechanisms regulating the energy balance was also noted. However, the proportion of explained variance for BMI is still low, suggesting other mechanisms such as gene-gene and gene-environment interactions, rare gene variants, copy number variants polymorphisms, or epigenetic modifications and microRNAs regulating gene transcription. In summary, we present results of our studies on obesity risk variants in Czech adults, children and adolescents including those evaluating the influence of selected gene variants on the outcomes of weight management.

  13. Rhizobium ecuadorense sp. nov., an indigenous N2-fixing symbiont of the Ecuadorian common bean (Phaseolus vulgaris L.) genetic pool.

    Science.gov (United States)

    Ribeiro, Renan Augusto; Martins, Talita Busulini; Ormeño-Orrillo, Ernesto; Marçon Delamuta, Jakeline Renata; Rogel, Marco Antonio; Martínez-Romero, Esperanza; Hungria, Mariangela

    2015-09-01

    There are two major centres of genetic diversification of common bean (Phaseolus vilgaris L.), the Mesoamerican and the Andean, and the legume is capable of establishing nitrogen-fixing symbioses with several rhizobia; Rhizobium etli seems to be the dominant species in both centres. Another genetic pool of common bean, in Peru and Ecuador, is receiving increasing attention, and studies of microsymbionts from the region can help to increase our knowledge about coevolution of this symbiosis. We have previously reported several putative new lineages from this region and here present data indicating that strains belonging to one of them, PEL4, represent a novel species. Based on 16S rRNA gene sequence phylogeny, PEL4 strains are positioned in the Rhizobium phaseoli/R. etli/Rhizobium leguminosarum clade, but show unique properties in several morphological, physiological and biochemical analyses, as well as in BOX-PCR profiles ( Rhizobium fabae. DNA-DNA hybridization ( Rhizobium ecuadorense sp. nov. The type strain is CNPSo 671(T) ( = UMR 1450(T) = PIMAMPIRS I 5(T) = LMG 27578(T)).

  14. Molecular genetic analysis of grain protein content and flour whiteness degree using RILs in common wheat

    Indian Academy of Sciences (India)

    XIANYIN SUN; KE WU; YAN ZHAO; ZHAOGUO QIAN; FANMEI KONG; YING GUO; YINGYING WANG; SISHEN LI

    2016-06-01

    Grain protein content (GPC) and flour whiteness degree (FWD) are important qualitative traits in common wheat. Quantitativetrait locus (QTL) mapping for GPC and FWD was conducted using a set of 131 recombinant-inbred lines derived fromthe cross ‘Chuan 35050 ×Shannong 483’ in six environmental conditions. A total of 22 putative QTLs (nine GPC and13 FWD) were identified on 12 chromosomes with individual QTL explaining 4.5–34.0% phenotypic variation. Nine QTLs(40.9%) were detected in two or more environments. The colocated QTLs were on chromosomes 1B and 4B. Among theQTLs identified for GPC,QGpc.sdau-4Afrom the parent Shannong 483 represented some important favourable QTL alleles.QGpc.sdau-2A.1andQFwd.sdau-2A.1had a significant association with both GPC and FWD. The markers detected on topof QTL regions could be potential targets for marker-assisted selection.

  15. One Community’s Effort to Control Genetic Disease

    Science.gov (United States)

    Puffenberger, Erik G.; Morton, D. Holmes

    2012-01-01

    In 1989, we established a small community health clinic to provide care for uninsured Amish and Mennonite children with genetic disorders. Over 20 years, we have used publicly available molecular data and sophisticated technologies to improve diagnostic efficiency, control laboratory costs, reduce hospitalizations, and prevent major neurological impairments within a rural underserved community. These actions allowed the clinic’s 2010 operating budget of $1.5 million to save local communities an estimated $20 to $25 million in aggregate medical costs. This exposes an unsettling fact: our failure to improve the lot of most people stricken with genetic disease is no longer a matter of scientific ignorance or prohibitive costs but of choices we make about how to implement existing knowledge and resources. PMID:22594747

  16. Genetic diversity of common bean accessions from former Yugoslav Republic of Macedonia as revealed by molecular and morphological markers

    Directory of Open Access Journals (Sweden)

    Maras Marko

    2016-01-01

    Full Text Available Cultivation of common bean has a long tradition in the Former Yugoslav Republic of Macedonia (FYROM and is still nowadays important part of the human diet. In a study reported here 71 accessions from the FYROM were assessed for genetic diversity with the aim to provide information on genetic structure of Macedonian common bean germplasm and to depict its peculiarities. A total of 71 accessions were assessed using 13 microsatellite and 16 morphological markers. The average number of alleles per microsatellite was 5.8, and ranged from three to 16 alleles. High capacity of selected markers for distinguishing genotypes was identified by the calculation of a very low value of probability of identity. The relationship among 71 studied accessions was assessed by hierarchical cluster analysis. A very clear separation of accessions into two groups was observed in the UPGMA dendrogram. The larger represented Andean gene pool and contained 40 accessions (56% of total, while the other 31 accessions (44% of total composed Mesoamerican gene pool. The two groups were successfully discriminated by eight morphological traits. Within the larger Andean cluster in the UPGMA dendrogram a sub-group of 16 climbing accessions was separated from 24 bush accessions. The absence of the string in the pods of the climbers suggests that this sub-group comprises snap beans grown primarily for their fresh pods. There were eight morphological traits in total that distinguished the two Andean sub-groups. Assessment of genetic relationship among accessions, their classification into respective gene pool and identification of morphological peculiarities provided valuable information for the management of plant gene bank and Macedonian bean breeding program.

  17. Origin of the Genetic Components of the Vomeronasal System in the Common Ancestor of all Extant Vertebrates

    Science.gov (United States)

    Grus, Wendy E.; Zhang, Jianzhi

    2009-01-01

    Comparative genomics provides a valuable tool for inferring the evolutionary history of physiological systems, particularly when this information is difficult to ascertain by morphological traits. One such example is the vomeronasal system (VNS), a vertebrate nasal chemosensory system that is responsible for detecting intraspecific pheromonal cues as well as environmental odorants. The morphological components of the VNS are found only in tetrapods, but the genetic components of the system have been found in teleost fish, in addition to tetrapods. To determine when the genetic components of the VNS originated, we searched for the VNS-specific genes in the genomes of two early diverging vertebrate lineages: the sea lamprey from jawless fishes and the elephant shark from cartilaginous fishes. Genes encoding vomeronasal type 1 receptors (V1Rs) and Trpc2, two components of the vomeronasal signaling pathway, are present in the sea lamprey genome, and both are expressed in the olfactory organ, revealing that the genetic components of the present-day VNS existed in the common ancestor of all extant vertebrates. Additionally, all three VNS genes, Trpc2, V1Rs, and vomeronasal type 2 receptors (V2Rs), are found in the elephant shark genome. Because V1Rs and V2Rs are related to two families of taste receptors, we also searched the early diverging vertebrate genomes for taste system genes and found them in the shark genome but not in the lamprey. Coupled with known distributions of the genetic components of the vertebrate main olfactory system, our results suggest staggered origins of vertebrate sensory systems. These findings are important for understanding the evolution of vertebrate sensory systems and illustrate the utility of the genome sequences of early diverging vertebrates for uncovering the evolution of vertebrate-specific traits. PMID:19008528

  18. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

    DEFF Research Database (Denmark)

    Jim, Heather S L; Lin, Hui-Yi; Tyrer, Jonathan P

    2015-01-01

    single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2......,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant...... where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine...

  19. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

    DEFF Research Database (Denmark)

    Jim, Heather S L; Lin, Hui-Yi; Tyrer, Jonathan P

    2016-01-01

    single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2......,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant...... where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine...

  20. Heme Oxygenase-1 and 2 Common Genetic Variants and Risk for Restless Legs Syndrome.

    Science.gov (United States)

    García-Martín, Elena; Jiménez-Jiménez, Félix Javier; Alonso-Navarro, Hortensia; Martínez, Carmen; Zurdo, Martín; Turpín-Fenoll, Laura; Millán-Pascual, Jorge; Adeva-Bartolomé, Teresa; Cubo, Esther; Navacerrada, Francisco; Rojo-Sebastián, Ana; Rubio, Lluisa; Ortega-Cubero, Sara; Pastor, Pau; Calleja, Marisol; Plaza-Nieto, José Francisco; Pilo-de-la-Fuente, Belén; Arroyo-Solera, Margarita; García-Albea, Esteban; Agúndez, José A G

    2015-08-01

    Several neurochemical, neuropathological, neuroimaging, and experimental data, suggest that iron deficiency plays an important role in the pathophysiology of restless legs syndrome (RLS). Heme-oxygenases (HMOX) are an important defensive mechanism against oxidative stress, mainly through the degradation of heme to biliverdin, free iron, and carbon monoxide. We analyzed whether HMOX1 and HMOX2 genes are related with the risk to develop RLS.We analyzed the distribution of genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number variations (CNVs) of these genes in 205 subjects RLS and 445 healthy controls.The frequencies of rs2071746TT genotype and rs2071746T allelic variant were significantly lower in RLS patients than that in controls, although the other 3 studied SNPs did not differ between RLS patients and controls. None of the studied polymorphisms influenced the disease onset, severity of RLS, family history of RLS, serum ferritin levels, or response to dopaminergic agonist, clonazepam or GABAergic drugs.The present study suggests a weak association between HMOX1 rs2071746 polymorphism and the risk to develop RLS in the Spanish population.

  1. SNP discovery in common bean by restriction-associated DNA (RAD) sequencing for genetic diversity and population structure analysis.

    Science.gov (United States)

    Valdisser, Paula Arielle M R; Pappas, Georgios J; de Menezes, Ivandilson P P; Müller, Bárbara S F; Pereira, Wendell J; Narciso, Marcelo G; Brondani, Claudio; Souza, Thiago L P O; Borba, Tereza C O; Vianello, Rosana P

    2016-06-01

    Researchers have made great advances into the development and application of genomic approaches for common beans, creating opportunities to driving more real and applicable strategies for sustainable management of the genetic resource towards plant breeding. This work provides useful polymorphic single-nucleotide polymorphisms (SNPs) for high-throughput common bean genotyping developed by RAD (restriction site-associated DNA) sequencing. The RAD tags were generated from DNA pooled from 12 common bean genotypes, including breeding lines of different gene pools and market classes. The aligned sequences identified 23,748 putative RAD-SNPs, of which 3357 were adequate for genotyping; 1032 RAD-SNPs with the highest ADT (assay design tool) score are presented in this article. The RAD-SNPs were structurally annotated in different coding (47.00 %) and non-coding (53.00 %) sequence components of genes. A subset of 384 RAD-SNPs with broad genome distribution was used to genotype a diverse panel of 95 common bean germplasms and revealed a successful amplification rate of 96.6 %, showing 73 % of polymorphic SNPs within the Andean group and 83 % in the Mesoamerican group. A slightly increased He (0.161, n = 21) value was estimated for the Andean gene pool, compared to the Mesoamerican group (0.156, n = 74). For the linkage disequilibrium (LD) analysis, from a group of 580 SNPs (289 RAD-SNPs and 291 BARC-SNPs) genotyped for the same set of genotypes, 70.2 % were in LD, decreasing to 0.10 %in the Andean group and 0.77 % in the Mesoamerican group. Haplotype patterns spanning 310 Mb of the genome (60 %) were characterized in samples from different origins. However, the haplotype frameworks were under-represented for the Andean (7.85 %) and Mesoamerican (5.55 %) gene pools separately. In conclusion, RAD sequencing allowed the discovery of hundreds of useful SNPs for broad genetic analysis of common bean germplasm. From now, this approach provides an excellent panel

  2. Genetic Algorithm and Fuzzy Tuning PID Controller Applied on Speed Control System for Marine Diesel Engines

    Directory of Open Access Journals (Sweden)

    Naeim Farouk

    2012-11-01

    Full Text Available The degree of speed control of ship machinery effects on the economics and optimization of the machinery configuration and operation. All marine vessel ranging need some sort of speed control system to control and govern the speed of the marine diesel engines. The main focus of this study is to apply and comparative between two specific soft-computing techniques. Fuzzy logic controller and genetic algorithm to design and tuning of PID controller for applied on speed control system of marine diesel engine to get an output with better dynamic and static performance. Simulation results show that the response of system when using genetic algorithm is better and faster than when using fuzzy tuning PID controller.

  3. [Genetics of congenital color vision defects. I. Common types of color blindness].

    Science.gov (United States)

    Krawczyński, M R

    1995-01-01

    Normal human colour vision is based on the presence of 3 kinds of cones containing 3 different visual pigments, sensitive to short (blue), middle (green) and long (red) wavelengths. Congenital defects of colour vision are based on handicap or total loss of these pigments' function, usually a result of changes in their coding genes. The common types of colour blindness, referred to red-green axis, are present in about 8% of males and 0.44% of females. 3/4 of them are deuteranopes or deuteranomalous trichromats and 1/4 of them are protanopes or protanomalous trichromats. All of them are inherited in X-linked recessive way. The genes have been already mapped and sequenced. The cause of the great majority of their changes is nonhomologous recombination, which produces a gene deletion or creates the red-green or green-red hybrid genes. The result of that is the production of visual pigment with partly or totally changed spectral sensitivity.

  4. Genetic analysis of the resistance to eight anthracnose races in the common bean differential cultivar Kaboon.

    Science.gov (United States)

    Campa, Ana; Giraldez, Ramón; Ferreira, Juan José

    2011-06-01

    Resistance to the eight races (3, 7, 19, 31, 81, 449, 453, and 1545) of the pathogenic fungus Colletotrichum lindemuthianum (anthracnose) was evaluated in F(3) families derived from the cross between the anthracnose differential bean cultivars Kaboon and Michelite. Molecular marker analyses were carried out in the F(2) individuals in order to map and characterize the anthracnose resistance genes or gene clusters present in Kaboon. The analysis of the combined segregations indicates that the resistance present in Kaboon against these eight anthracnose races is determined by 13 different race-specific genes grouped in three clusters. One of these clusters, corresponding to locus Co-1 in linkage group (LG) 1, carries two dominant genes conferring specific resistance to races 81 and 1545, respectively, and a gene necessary (dominant complementary gene) for the specific resistance to race 31. A second cluster, corresponding to locus Co-3/9 in LG 4, carries six dominant genes conferring specific resistance to races 3, 7, 19, 449, 453, and 1545, respectively, and the second dominant complementary gene for the specific resistance to race 31. A third cluster of unknown location carries three dominant genes conferring specific resistance to races 449, 453, and 1545, respectively. This is the first time that two anthracnose resistance genes with a complementary mode of action have been mapped in common bean and their relationship with previously known Co- resistance genes established.

  5. Disease and Polygenic Architecture: Avoid Trio Design and Appropriately Account for Unscreened Control Subjects for Common Disease

    Science.gov (United States)

    Peyrot, Wouter J.; Boomsma, Dorret I.; Penninx, Brenda W.J.H.; Wray, Naomi R.

    2016-01-01

    Genome-wide association studies (GWASs) are an optimal design for discovery of disease risk loci for diseases whose underlying genetic architecture includes many common causal loci of small effect (a polygenic architecture). We consider two designs that deserve careful consideration if the true underlying genetic architecture of the trait is polygenic: parent-offspring trios and unscreened control subjects. We assess these designs in terms of quantification of the total contribution of genome-wide genetic markers to disease risk (SNP heritability) and power to detect an associated risk allele. First, we show that trio designs should be avoided when: (1) the disease has a lifetime risk > 1%; (2) trio probands are ascertained from families with more than one affected sibling under which scenario the SNP heritability can drop by more than 50% and power can drop as much as from 0.9 to 0.15 for a sample of 20,000 subjects; or (3) assortative mating occurs (spouse correlation of the underlying liability to the disorder), which decreases the SNP heritability but not the power to detect a single locus in the trio design. Some studies use unscreened rather than screened control subjects because these can be easier to collect; we show that the estimated SNP heritability should then be scaled by dividing by (1 − K × u)2 for disorders with population prevalence K and proportion of unscreened control subjects u. When omitting to scale appropriately, the SNP heritability of, for example, major depressive disorder (K = 0.15) would be underestimated by 28% when none of the control subjects are screened. PMID:26849113

  6. 常见线粒体DNA病的分子遗传学研究进展%Molecular genetics of common mitochondrial DNA disorders

    Institute of Scientific and Technical Information of China (English)

    Lee-Jun C. WONG

    2005-01-01

    SUMMARY Diagnosis of mitochondrial disorders has been difficult due to the clinical and genetic heterogeneity, as well as unique features of mitochondrial genetics. Definitive diagnosis requires the identification of molecular defects in either the mitochondrial or the nuclear genome. We describe the clinical and molecular characteristic of some common mitochondrial syndromes and molecular methodologies available for the detection of mitochondrial DNA mutations. This review provides overview of current molecular diagnosis of mitochondrial DNA disorders that is useful in patient care and genetic counseling.

  7. Application of Improved Genetic Algorithm in PID Controller Parameters Optimization

    Directory of Open Access Journals (Sweden)

    Ying Chen

    2013-01-01

    Full Text Available Ying Chen, Yong-jie Ma, Wen-xia Yun College of Physics and Electronic Engineering, Northwest Normal University, Anning Road no.967 ,Lanzhou,China,0931-7971503 e-mail:chenying1386685@126.com Abstract The setting and optimization of Proportion Integration Differentiation(PID parameters have been always the important study topics in the automatic control field. The current optimization design methods are often difficult to consider the system requirements for quickness ,reliability and robustness .So a method of PID controller parameters optimization based on Improved Genetic Algorithm(IGA is presented .Simulations with Matlab have proved that the control performance index based on IGA is better than that of the GA method and Z-N method, and is a method which has good practical value of the PID parameter setting and optimization .

  8. Design of bounded feedback controls for linear dynamical systems by using common Lyapunov functions

    Institute of Scientific and Technical Information of China (English)

    Igor; Ananievskii; Nickolai; Anokhin; Alexander; Ovseevich

    2011-01-01

    For a linear dynamical system,we address the problem of devising a bounded feedback control,which brings the system to the origin in finite time.The construction is based on the notion of a common Lyapunov function.It is shown that the constructed control remains effective in the presence of small perturbations.

  9. Genetic based sensorless hybrid intelligent controller for strip loop formation control between inter-stands in hot steel rolling mills.

    Science.gov (United States)

    Thangavel, S; Palanisamy, V; Duraiswamy, K

    2008-04-01

    Safe operating environment is essential for all complex industrial processes. The safety issues in steel rolling mill when the hot strip passes through consecutive mill stands have been considered in this paper. Formation of sag in strip is a common problem in the rolling process. The excessive sag can lead to scrap runs and damage to machinery. Conventional controllers for mill actuation system are based on a rolling model. The factors like rise in temperature, aging, wear and tear are not taken into account while designing a conventional controller. Therefore, the conventional controller cannot yield a requisite controlled output. In this paper, a new Genetic-neuro-fuzzy hybrid controller without tension sensor has been proposed to optimize the quantum of excessive sag and reduce it. The performance of the proposed controller has been compared with the performance of fuzzy logic controller, Neuro-fuzzy controller and conventional controller with the help of data collected from the plant. The simulation results depict that the proposed controller has superior performance than the other controllers.

  10. Attitude control of an object commonly held by multiple robot arms - A Lyapunov approach

    Science.gov (United States)

    Kreutz, Kenneth; Wen, John T.

    1988-01-01

    Multiple robot arms moving a commonly held object can be viewed as complex actuators whose purpose is to provide net forces and moments to the object. These forces and moments can be used to control the orientation, or attitude, of the object via the Euler equation describing attitude evolution in response to applied moments at the mass center. In contrast to the common approach that feedback-linearizes the attitude dynamics to a double integrator form with respect to some three-parameter local representation of orientation, the authors control the object using a globally nonsingular representation. Using an energy-motivated Liapunov function, globally stable control of attitude is shown.

  11. Attitude control of an object commonly held by multiple robot arms - A Lyapunov approach

    Science.gov (United States)

    Kreutz, Kenneth; Wen, John T.

    1988-01-01

    Multiple robot arms moving a commonly held object can be viewed as complex actuators whose purpose is to provide net forces and moments to the object. These forces and moments can be used to control the orientation, or attitude, of the object via the Euler equation describing attitude evolution in response to applied moments at the mass center. In contrast to the common approach that feedback-linearizes the attitude dynamics to a double integrator form with respect to some three-parameter local representation of orientation, the authors control the object using a globally nonsingular representation. Using an energy-motivated Liapunov function, globally stable control of attitude is shown.

  12. Genetic and systems level analysis of Drosophila sticky/citron kinase and dFmr1 mutants reveals common regulation of genetic networks

    Directory of Open Access Journals (Sweden)

    Zarnescu Daniela C

    2008-11-01

    Full Text Available Abstract Background In Drosophila, the genes sticky and dFmr1 have both been shown to regulate cytoskeletal dynamics and chromatin structure. These genes also genetically interact with Argonaute family microRNA regulators. Furthermore, in mammalian systems, both genes have been implicated in neuronal development. Given these genetic and functional similarities, we tested Drosophila sticky and dFmr1 for a genetic interaction and measured whole genome expression in both mutants to assess similarities in gene regulation. Results We found that sticky mutations can dominantly suppress a dFmr1 gain-of-function phenotype in the developing eye, while phenotypes produced by RNAi knock-down of sticky were enhanced by dFmr1 RNAi and a dFmr1 loss-of-function mutation. We also identified a large number of transcripts that were misexpressed in both mutants suggesting that sticky and dFmr1 gene products similarly regulate gene expression. By integrating gene expression data with a protein-protein interaction network, we found that mutations in sticky and dFmr1 resulted in misexpression of common gene networks, and consequently predicted additional specific phenotypes previously not known to be associated with either gene. Further phenotypic analyses validated these predictions. Conclusion These findings establish a functional link between two previously unrelated genes. Microarray analysis indicates that sticky and dFmr1 are both required for regulation of many developmental genes in a variety of cell types. The diversity of transcripts regulated by these two genes suggests a clear cause of the pleiotropy that sticky and dFmr1 mutants display and provides many novel, testable hypotheses about the functions of these genes. As both of these genes are implicated in the development and function of the mammalian brain, these results have relevance to human health as well as to understanding more general biological processes.

  13. Genetic and epigenetic control of plant heat responses

    Directory of Open Access Journals (Sweden)

    Junzhong eLiu

    2015-04-01

    Full Text Available Plants have evolved sophisticated genetic and epigenetic regulatory systems to respond quickly to unfavorable environmental conditions such as heat, cold, drought, and pathogen infections. In particular, heat greatly affects plant growth and development, immunity and circadian rhythm, and poses a serious threat to the global food supply. According to temperatures exposing, heat can be usually classified as warm ambient temperature (about 22-27℃, high temperature (27-30℃ and extremely high temperature (37-42℃, also known as heat stress for the model plant Arabidopsis thaliana. The genetic mechanisms of plant responses to heat have been well studied, mainly focusing on elevated ambient temperature-mediated morphological acclimation and acceleration of flowering, modulation of plant immunity and circadian clock by high temperatures, and thermotolerance to heat stress. Recently, great progress has been achieved on epigenetic regulation of heat responses, including DNA methylation, histone modifications, histone variants, ATP-dependent chromatin remodeling, histone chaperones, small RNAs, long non-coding RNAs and other undefined epigenetic mechanisms. These epigenetic modifications regulate the expression of heat-responsive genes and function to prevent heat-related damage. This review focuses on recent progresses regarding the genetic and epigenetic control of heat responses in plants, and pays more attention to the role of the major epigenetic mechanisms in plant heat responses. Further research perspectives are also discussed.

  14. Manipulator Neural Network Control Based on Fuzzy Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The three-layer forward neural networks are used to establish the inverse kinem a tics models of robot manipulators. The fuzzy genetic algorithm based on the line ar scaling of the fitness value is presented to update the weights of neural net works. To increase the search speed of the algorithm, the crossover probability and the mutation probability are adjusted through fuzzy control and the fitness is modified by the linear scaling method in FGA. Simulations show that the propo sed method improves considerably the precision of the inverse kinematics solutio ns for robot manipulators and guarantees a rapid global convergence and overcome s the drawbacks of SGA and the BP algorithm.

  15. Control of the lighting system using a genetic algorithm

    Directory of Open Access Journals (Sweden)

    Čongradac Velimir D.

    2012-01-01

    Full Text Available The manufacturing, distribution and use of electricity are of fundamental importance for the social life and they have the biggest influence on the environment associated with any human activity. The energy needed for building lighting makes up 20-40% of the total consumption. This paper displays the development of the mathematical model and genetic algorithm for the control of dimmable lighting on problems of regulating the level of internal lighting and increase of energetic efficiency using daylight. A series of experiments using the optimization algorithm on the realized model confirmed very high savings in electricity consumption.

  16. Genetic control of immune responsiveness in the chicken

    NARCIS (Netherlands)

    Zijpp, van der A.J.

    1982-01-01

    Disease can be combated by medication, vaccination, hygienic measures, eradication and genetic resistance. Genetic resistance to infectious diseases is advantageous because of its permanent character in contrast with the aforementioned procedures. In the chicken genetic resistance to specific diseas

  17. Common genetic variations in CLOCK transcription factor are associated with nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Silvia Sookoian; Gustavo Casta(n)o; Carolina Gemma; Tomas Fernández Gianotti; Carlos Jose Pirola

    2007-01-01

    AIM: To investigate the role of gene variants and derived haplotypes of the CLOCK transcription factor in nonalcoholic fatty liver disease (NAFLD) and their relation with the disease severity.METHODS: A total of 136 patients with NAFLD and 64 healthy individuals were studied. Liver biopsy was performed in 91 patients. Six tag SNPs showing a minor allele frequency > 10% (rs1554483 C/G; rs11932595A/G; rs4580704 C/G; rs6843722 A/C; rs6850524 C/G and rs4864548 A/G) encompassing 117 kb of chromosome 4and representing 115 polymorphic sites (r2>0.8) were genotyped.RESULTS: rs11932595 and rs6843722 showed significant associations with NAFLD (empiric P = 0.0449and 0.023, respectively). A significant association was also observed between clinical or histologic spectrum of NAFLD and rs1554483 (empiric P = 0.0399), rs6843722(empiric P = 0.0229) and rs6850524 (empiric P =0.00899) and between fibrosis score and rs1554483(empiric P = 0.02697), rs6843722 (empiric P = 0.01898)and rs4864548 (empiric P = 0.02697). Test of haplotypic association showed that CLOCK gene variant haplotypes frequencies in NAFLD individuals significantly differed from those in controls (empiric P = 0.0097).CONCLUSION: Our study suggests a potential role of the CLOCK polymorphisms and their haplotypes in susceptibility to NAFLD and disease severity.

  18. Genetic depletion of brain 5HT reveals a common molecular pathway mediating compulsivity and impulsivity.

    Science.gov (United States)

    Angoa-Pérez, Mariana; Kane, Michael J; Briggs, Denise I; Sykes, Catherine E; Shah, Mrudang M; Francescutti, Dina M; Rosenberg, David R; Thomas, David M; Kuhn, Donald M

    2012-06-01

    Neuropsychiatric disorders characterized by behavioral disinhibition, including disorders of compulsivity (e.g. obsessive-compulsive disorder; OCD) and impulse-control (e.g. impulsive aggression), are severe, highly prevalent and chronically disabling. Treatment options for these diseases are extremely limited. The pathophysiological bases of disorders of behavioral disinhibition are poorly understood but it has been suggested that serotonin dysfunction may play a role. Mice lacking the gene encoding brain tryptophan hydroxylase 2 (Tph2-/-), the initial and rate-limiting enzyme in the synthesis of serotonin, were tested in numerous behavioral assays that are well known for their utility in modeling human neuropsychiatric diseases. Mice lacking Tph2 (and brain 5HT) show intense compulsive and impulsive behaviors to include extreme aggression. The impulsivity is motor in form and not cognitive because Tph2-/- mice show normal acquisition and reversal learning on a spatial learning task. Restoration of 5HT levels by treatment of Tph2-/- mice with its immediate precursor 5-hydroxytryptophan attenuated compulsive and impulsive-aggressive behaviors. Surprisingly, in Tph2-/- mice, the lack of 5HT was not associated with anxiety-like behaviors. The results indicate that 5HT mediates behavioral disinhibition in the mammalian brain independent of anxiogenesis.

  19. Convergence Rate Evaluation of a DS-CDMA System with Centralized Power Control By Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In this paper, we propose an approach to solve the power control issue in a Digital Cellular System(DS-CDMA) cellular system using Genetic Algorithms (GAs). The transmitter power control developed in this paper has been proven to be efficient to control co-channel interference, to increase bandwidth utilization and to balance the comprehensive services that are shared among all the mobiles with attaining a common Signal-to-Interference Ratio (SIR). In this paper, the optimal Centralized Power Control(CPC) vector is characterized and its optimal solution to CPC is presented using GAs, in which First In-First Out (FIFO) stacks and non-linear decreasing functions are derived in the investigation for enforceing the convergence rate. Emphasis is put on the balance of services and convergence rate by using GAs.

  20. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC Risk.

    Directory of Open Access Journals (Sweden)

    Ganna Chornokur

    Full Text Available Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC, we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC. Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS. SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020; this SNP was also associated with the borderline/low malignant potential (LMP tumors (P = 0.021. Other genes significantly associated with EOC histological subtypes (p<0.05 included the UGT1A (endometrioid, SLC25A45 (mucinous, SLC39A11 (low malignant potential, and SERPINA7 (clear cell carcinoma. In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4.These results, generated on a large cohort of women, revealed associations between inherited cellular

  1. Common MIR146A Polymorphisms in Chinese Ankylosing Spondylitis Subjects and Controls.

    Directory of Open Access Journals (Sweden)

    Zhenmin Niu

    Full Text Available Common polymorphisms of microRNA gene MIR146A were reported as associated with different autoimmune diseases, include systemic lupus erythematosus, psoriatic arthritis, asthma and ankylosing spondylitis. In this study we investigated MIR146A SNPs in Chinese people with ankylosing spondylitis. Three common SNPs: rs2910164, rs2431697 and rs57095329 were selected and genotyped in 611 patients and 617 controls. We found no association between these SNPs and ankylosing spondylitis in our samples.

  2. Common genetic variation near MC4R has a sex-specific impact on human brain structure and eating behavior.

    Directory of Open Access Journals (Sweden)

    Annette Horstmann

    Full Text Available Obesity is associated with genetic and environmental factors but the underlying mechanisms remain poorly understood. Recent genome-wide association studies (GWAS identified obesity- and type 2 diabetes-associated genetic variants located within or near genes that modulate brain activity and development. Among the top hits is rs17782313 near MC4R, encoding for the melanocortin-4-receptor, which is expressed in brain regions that regulate eating. Here, we hypothesized rs17782313-associated changes in human brain regions that regulate eating behavior. Therefore, we examined effects of common variants at rs17782313 near MC4R on brain structure and eating behavior. Only in female homozygous carriers of the risk allele we found significant increases of gray matter volume (GMV in the right amygdala, a region known to influence eating behavior, and the right hippocampus, a structure crucial for memory formation and learning. Further, we found bilateral increases in medial orbitofrontal cortex, a multimodal brain structure encoding the subjective value of reinforcers, and bilateral prefrontal cortex, a higher order regulation area. There was no association between rs17782313 and brain structure in men. Moreover, among female subjects only, we observed a significant increase of 'disinhibition', and, more specifically, on 'emotional eating' scores of the Three Factor Eating Questionnaire in carriers of the variant rs17782313's risk allele. These findings suggest that rs17782313's effect on eating behavior is mediated by central mechanisms and that these effects are sex-specific.

  3. How genetics research in Parkinson's disease is enhancing understanding of the common idiopathic forms of the disease.

    Science.gov (United States)

    Cookson, Mark R; Xiromerisiou, Georgia; Singleton, Andrew

    2005-12-01

    Rapid progress in genetics