Página 6 dos resultados de 46671 itens digitais encontrados em 0.029 segundos

The current state of play on the molecular genetics of depression

Cohen-Woods, S.; Craig, I.; McGuffin, P.
Fonte: Cambridge University Press Publicador: Cambridge University Press
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
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BACKGROUND: It has been well established that both genes and non-shared environment contribute substantially to the underlying aetiology of major depressive disorder (MDD). A comprehensive overview of genetic research in MDD is presented. Method Papers were retrieved from PubMed up to December 2011, using many keywords including: depression, major depressive disorder, genetics, rare variants, gene-environment, whole genome, epigenetics, and specific candidate genes and variants. These were combined in a variety of permutations. RESULTS: Linkage studies have yielded some promising chromosomal regions in MDD. However, there is a continued lack of consistency in association studies, in both candidate gene and genome-wide association studies (GWAS). Numerous factors may account for variable results including the use of different diagnostic approaches, small samples in early studies, population stratification, epigenetic phenomena, copy number variation (CNV), rare variation, and phenotypic and allelic heterogeneity. The conflicting results are also probably, in part, a consequence of environmental factors not being considered or controlled for. CONCLUSIONS: Each research group has to identify what issues their sample may best address. We suggest that...

Systems genetics analysis reveals gene modules and heritable biomarkers for sheep intestinal parasite resistance

Kadarmideen, H.N.; Andronicos, N.; Watson-Haigh, N.
Fonte: Association for the Advancement of Animal Breeding and Genetics; Australia Publicador: Association for the Advancement of Animal Breeding and Genetics; Australia
Tipo: Conference paper
Publicado em //2009 EN
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Systems genetics methods were applied to microarray gene expression profiling data from a sheep gastrointestinal nematode (GIN) challenge experiment that was designed to detect genes associated with resistance to GIN. Analyses went beyond just detecting and annotating differentially expressed (DE) genes. This included detection of co-expressed (CE) gene modules associated with the duration of infection, essential hub genes, functional enrichment and pathway analyses. Results revealed that DE genes were highly enriched in functions such as cell-mediated and humoral immunological response to GIN. Further, heritabilities were estimated for expression phenotypes of such candidate biomarkers (range 0.05 to 0.9 with high s.e.) indicating their potential for expression-assisted selection. Hence, the systems genetics method is a key step in identifying biologically relevant and heritable genes/biomarkers amongst several sets of DE genes. This approach would provide specific targets for breeding and therapeutic interventions.; H. N. Kadarmideen, N. Andronicos, and N. S. Watson-Haigh

Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables

Thompson, S.; Burgess, S.; CRP CHD Genetics Collaboration
Fonte: John Wiley & Sons Ltd Publicador: John Wiley & Sons Ltd
Tipo: Artigo de Revista Científica
Publicado em //2010 EN
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Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias...

Perspectives of genetics for man.

Tavares, Amândio S.; Department of General Pathology and Genetics, Faculty of Medicine. Oporto. Portugal
Fonte: Ordem dos Médicos Publicador: Ordem dos Médicos
Tipo: info:eu-repo/semantics/article; article; article; info:eu-repo/semantics/publishedVersion Formato: application/pdf
Publicado em 01/07/1979 POR
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The human species attained a high technological development, which enables it to induce important alterations in jts environment and in the parameters of its own evolution. Genetics p!ays an important role in the study of such influences and in the solution of present problems of Mankind, as relates its future, genetic load and subsistence. The present objective of Genetics, as applied to the human being, is to understand what is inherited (and in what proportion). Hereditary diseases tend to occupy an important place among pathological entities and the physician’s objective, saving his patients, increases the genetic load of the population. adding a new stress to the human genome, already under the influence of social and cultural transformations. To analyse this effect, more data on human social biology are needed, as well as on the results of new medical and biological technologies. Genetic engineering, the study of biochemical polymorphisms and their eventual selective value, cytogenetic analysis of malformative syndromes or sexual maldevelopment and genetic counselling, should be developed and extended in the general population. However, genetic counselling should preserve the freedom of choice of the individual or the couple in order to avoid its transformation into a mere kind of eugenics and to maintain both the personality of those being at risk and the population’s genetic heteromorphism.

Unlocking the bottleneck in forward genetics using whole-genome sequencing and identity by descent to isolate causative mutations

Bull, Katherine R; Rimmer, Andrew J; Siggs, Owen M; Miosge, Lisa A; Roots, Carla M; Enders, Anselm; Bertram, Edward M; Crockford, Tanya L; Whittle, Belinda; Potter, Paul K; Simon, Michelle M; Mallon, Ann-Marie; Brown, Steve D M; Beutler, Bruce; Goodnow, C
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica Formato: 12 pages
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Forward genetics screens with N-ethyl-N-nitrosourea (ENU) provide a powerful way to illuminate gene function and generate mouse models of human disease; however, the identification of causative mutations remains a limiting step. Current strategies depend on conventional mapping, so the propagation of affected mice requires non-lethal screens; accurate tracking of phenotypes through pedigrees is complex and uncertain; out-crossing can introduce unexpected modifiers; and Sanger sequencing of candidate genes is inefficient. Here we show how these problems can be efficiently overcome using whole-genome sequencing (WGS) to detect the ENU mutations and then identify regions that are identical by descent (IBD) in multiple affected mice. In this strategy, we use a modification of the Lander-Green algorithm to isolate causative recessive and dominant mutations, even at low coverage, on a pure strain background. Analysis of the IBD regions also allows us to calculate the ENU mutation rate (1.54 mutations per Mb) and to model future strategies for genetic screens in mice. The introduction of this approach will accelerate the discovery of causal variants, permit broader and more informative lethal screens to be used, reduce animal costs, and herald a new era for ENU mutagenesis.; The High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics is funded by Wellcome Trust grant reference 090532/Z/09/Z and MRC Hub grant G0900747 91070. This study was supported by Wellcome Trust Strategic Award 082030 (CCG)...

Análise genética populacional de Prosopis rubriflora Hassl. ("Espinheiro") e Prosopis ruscifolia Griseb. ("Algaroba") (Leguminosae, Mimosoideae) em áreas de Chaco brasileiro = : Population genetics analysis of Prosopis rubriflora Hassl. ("Espinheiro") and Prosopis ruscifolia Griseb. ("Algaroba") (Leguminosae, Mimosoideae) in remnants of Brazilian Chaco; Population genetics analysis of Prosopis rubriflora Hassl. ("Espinheiro") and Prosopis ruscifolia Griseb. ("Algaroba") (Leguminosae, Mimosoideae) in remnants of Brazilian Chaco

Fábio de Matos Alves
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 28/11/2014 PT
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As áreas de Chaco em território sulamericano, representam a maior área de floresta seca contínua do continente. No Brasil, estas áreas são encontradas principalmente na porção sudeste do domínio, no estado de Mato Grosso do Sul, região sul-pantaneira. Talvez por serem áreas de pouca cobertura, o seu conhecimento ainda é incipiente. Embora novos projetos tenham sido realizados nestas áreas nos últimos anos, a sua crescente supressão pelas atividades de pecuária extensiva tem sido preocupante. Não há na região qualquer tipo de Unidade de Conservação a fim de preservar o patrimônio genético das espécies que lá ocorrem, muitas das quais têm sua distribuição limitada a esta fitofisionomia. Desta forma, estudos que visem o conhecimento da variabilidade genética ainda existente, principalmente em áreas em processo de degradação são fundamentais para o conhecimento da atual situação das populações existentes, para indicar métodos de conservação, bem como a propor políticas públicas visando a manutenção e conservação do Chaco brasileiro. A fim de efetuar estimativas da diversidade genética, o uso de marcadores moleculares tem sido empregado em diversos estudos de populações nas diversas formações vegetacionais...

The Utility of Comparative Genetics to Inform Breast Cancer Prevention Strategies

Gould, Michael N.
Fonte: Genetics Society of America Publicador: Genetics Society of America
Tipo: Artigo de Revista Científica
Publicado em /10/2009 EN
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My research seeks to aid in developing approaches to prevent breast cancer. This research evolved from our early empirical studies for discovering natural compounds with anticancer activities, coupled with clinical evaluation to a genetics-driven approach to prevention. This centers on the use of comparative genomics to discover risk-modifying alleles that could help define population and individual risk and also serve as potential prevention drugable targets to mitigate risk. Here, we initially fine map mammary cancer loci in a rat carcinogenesis model and then evaluate their human homologs in breast cancer case-control association studies. This approach has yielded promising results, including the finding that the compound rat QTL Mcs5a's human homologous region was associated with breast cancer risk. These and related findings have the potential to yield advancements both in translation-prevention research and in basic molecular genetics.

Evidence based medicine in practice: lessons from a Scottish clinical genetics project

Campbell, H.; Bradshaw, N.; Davidson, R.; Dean, J.; Goudie, D.; Holloway, S.; Porteous, M.
Fonte: BMJ Group Publicador: BMJ Group
Tipo: Artigo de Revista Científica
Publicado em /09/2000 EN
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OBJECTIVE—To establish national clinical guidelines and integrated care pathways for five conditions (tuberous sclerosis (TS), Huntington's disease (HD), myotonic dystrophy (MD), neurofibromatosis type 1 (NF1), and Marfan syndrome (MS)) and audit their use in Scotland.
DESIGN—Systematic review of published reports followed by consensus conferences to prepare clinical guidelines and integrated care pathways. Structured review of medical records before and after introduction of integrated care pathways to document changes in practice. Survey of staff views on procedures adopted.
SETTING—All four clinical genetics centres in Scotland.
RESULTS—Project resulted in reduced variation in practice across centres, improved data recording in medical records, and improved communication with other professional groups. A very poor evidence base for management of patients with the conditions studied was found.
CONCLUSIONS—A collaborative structure for undertaking clinical research would improve the evidence base for current practice. National discussion of the boundaries of responsibility of care for the long term management of patients with these disorders is required. The integrated care pathway approach shows promise as a means of facilitating the development of audit within clinical genetics services.


Keywords: clinical guidelines; audit; evidence based medicine; care pathways

Conservation genetics of the critically endangered Montseny brook newt (Calotriton arnoldi)

Valbuena Ureña, Emilio; Carrassón López de Letona, Maite
Fonte: [Barcelona] : Universitat Autònoma de Barcelona, Publicador: [Barcelona] : Universitat Autònoma de Barcelona,
Tipo: Tesis i dissertacions electròniques; info:eu-repo/semantics/doctoralThesis; info:eu-repo/semantics/publishedVersion
Publicado em //2015 ENG
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El tritó del Montseny (Calotriton arnoldi) és un dels vertebrats més amenaçats d'Europa i està classificat com en perill crític per la IUCN. Aquesta espècie és endèmica del Parc Natural del Montseny (NE de la Península Ibèrica) i es distribueix en set torrents propers geogràficament (superfície total de 8 km2). El seu hàbitat està fragmentat en dos sectors principals (oriental i occidental) a banda i banda de la vall del riu Tordera. El cens actual poblacional ha estat estimat en menys de 1.500 individus adults. L'objectiu principal d'aquesta tesi és proporcionar coneixements bàsics sobre la genètica del tritó del Montseny perquè siguin útils per a la conservació de l'espècie. Així, s'ha explorat la biogeografia de l'espècie (Capítol 1), s'ha dissenyat nous marcadors microsatèl·lits polimòrfics (Capítol 2), s'ha caracteritzat i estudiat l'estructura genètica de les seves poblacions (Capítol 3) i s'ha avaluat el programa ex situ (capítol 4 ), mitjançant l'anàlisi de dos gens, un mitocondrial i un nuclear, juntament amb 24 marcadors microsatèl·lits. Així, confirmem la validesa de les dues espècies de Calotriton. Malgrat que el rang de distribució del tritó del Montseny és limitat, C. arnoldi presenta un alt grau d'estructuració genètica. Les anàlisis morfològiques i moleculars suggereixen dos grups poblacionals geogràficament diferents...

Understanding the epigenome using system genetics

Timmer, Sander Willem
Fonte: University of Cambridge; European Bioinformatics Institute; Clare Hall Publicador: University of Cambridge; European Bioinformatics Institute; Clare Hall
Tipo: Thesis; doctoral; PhD
EN
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Genetics has been successful in associating DNA sequence variants to both dichotomous and continuous traits in a variety of organisms, from plant and farm animal studies to human disease. With the advent of high-throughput genotyping, there has been an almost routine gen- eration of genome-wide association studies (GWAS) between human disease traits and genomic regions. Despite this success, a particular frustration is that the majority of associated loci are in non-coding regions of the genome and thus interpretation is hard. To improve characterisation of non-coding regions, molecular as- says can be used as a phenotype, and subsequently be used to explain how genetics alter molecular mechanisms. In this thesis, the inter- play of three molecular assays that are involved in regulating gene expression is studied. On 60 individuals, several assays are performed: FAIRE-chip, CTCF- seq, RNA-seq and DNA-seq. In the first part, the discovery and characteristics of FAIRE-QTLs is presented. The identified FAIRE-QTLs show strong overlap with other molecular QTLs, histone modifications, and transcription factors. The second part consists of the integration of genome-wide molecu- lar assays in a human population to reconstruct the human epigenome. Each of the molecular assays is associated with each of the other assays to discover phenotype-to-phenotype correlations. Furthermore...

The evolutionary genetics of sexually selected plumage colour traits in the galliform birds

Nadeau, Nicola Jacqueline
Fonte: University of Cambridge; Department of Zoology; Clare College Publicador: University of Cambridge; Department of Zoology; Clare College
Tipo: Thesis; doctoral; PhD
EN
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Extravagant male plumage traits in birds are a classic example of sexual selection. However we know very little about the units that selection is acting upon, the genes themselves ? what are they and how are they influenced by sexual selection? In this study I focused on in the evolution and genetics of colouration the galliform birds. Several novel loci were used to create a well resolved phylogeny of this group. This was then used to investigate and reconstruct the evolution of sexual plumage dichromatism. Four pigmentation genes were sequenced in an array of galliform species. A measure of the rate of evolutionary change (dN/dS) at these loci was then compared between lineages with different strengths of sexual selection, using sexual dichromatism as the main index of sexual selection. I found evidence for sexual selection acting at the MC1R locus, in the form of a robust correlation between dN/dS and sexual plumage dichromatism that was not found at any of the other loci. I then went on to investigate the evolution and population genetics of MC1R in the grouse, focusing on the strongly dichromatic black grouse and the relatively monochromatic red grouse. I found some evidence for an adaptive change at this locus between these species. Finally I used a candidate gene approach to investigate the role of several genes in avian pigmentation using the Japanese quail (Coturnix japonica) as a model system. I found evidence that the avian agouti gene is involved in dorso-ventral pigmentation patterning and a regulatory mutation at this locus that produces a yellow phenotype. In addition point mutations at MC1R and TYRP1 were found to be responsible for producing pigmentation variants. I then compared the expression of several of these candidate genes in male and female common pheasants (Phasianus colchicus) and found lower TYRP1 expression in males. Knowledge of the genetic basis of secondary sexual traits and the action of sexual selection at this level could have important implications for our understanding of the process of sexual selection as a whole.; This work was funded by the Natural Environment Research Council under the Environmental Genomics programme [grant number NER/T/S/2002/00020].

Amici Curiae Brief for Academics in Law, Medicine, Health Policy, and Clinical Genetics in Support of Neither Party on Writ of Certiorari to the United States Court of Appeals for the Federal Circuit

Gold, E. Richard; Bubela, Tania; Cook-Deegan, Robert Mullan; Evans, James P.; Kinderlerer, Julian; Nicol, Dianne
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Outros
Publicado em 30/11/2012 EN_US
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Brief of Amici Curiae ("friend of the court") submitted by the Academics in Law, Medicine, Health Policy, and Clinical Genetics in support of a petition for a Writ of Certiorari to the United States Court of Appeals for the Federal Circuit.

The Genetics of Primary Open-Angle Glaucoma: A Complex Human Disease

Carnes, Megan
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2014
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Glaucoma is a chronic ocular neuropathy and a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) is the most common subtype with an estimated 2 million affected individuals in the Unites States. POAG is a heritable complex trait. Understanding the genetics of POAG may increase our ability to predict disease onset and help elucidate the underlying biological mechanisms responsible for the development of the disease. With this overall goal, three different approaches are presented here.

First, the genetics of an important POAG-associated trait, central corneal thickness (CCT), was investigated using genome-wide single nucleotide polymorphism (SNP) data available from the NEIGHBOR and GLAUGEN consortia to identify novel POAG candidate genes. Twenty previously published CCT-associated SNPs were tested for association with both CCT (N = 1,117) and POAG (N = 6,470). While several of these variants were significantly associated with CCT in our dataset (top SNP = rs12447690, near ZNF469 (beta = -5.08 µm/allele; p = 0.001), none were associated with POAG. A CCT genome-wide association study was conducted. Using a p-value threshold of

1X10-4, 50 candidate SNPs were tested for association with POAG. One SNP...

Genetics and Biomarkers of Osteoarthritis and Joint Hypermobility

Chen, Hsiang-Cheng
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação Formato: 1892122 bytes; application/pdf
Publicado em //2009 EN_US
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Osteoarthritis (OA) is the most common joint disorder causing chronic disability in the world population. By the year 2030, an estimated one fifth of this population will be affected by OA. Although OA is regarded as a multi-factorial disorder with both environmental and genetic components, the exact pathogenesis remains unknown.

In this study, we hypothesize that biomarkers associated with OA can be used as quantitative traits of OA, and provide enough power to identify new genes or replicate known gene associations for OA. We established an extensive family called the CARRIAGE (CARolinas Region Interaction of Aging, Genes and Environment) family. Then, we measured and analyzed seven OA-related biomarkers (HA, COMP, PIIANP, CPII, C2C, hs-CRP and GSP) in this extensive family to evaluate their association with OA clinical phenotypes. These findings suggest that OA biomarkers can reflect hand OA in this large multigenerational family. Therefore, we performed nonparametric variance components analysis to evaluate heritability for quantitative traits for those biomarkers. Finally, based upon OA biomarkers with high heritability, we performed a genome-wide linkage scan. Our results provide the first evidence of genetic susceptibility loci identified by OA-related biomarkers...

Document granting Certiorari to case 12-398, Assoc. for Molecular Pathology v. Myriad Genetics, Inc, et al

Supreme Court of the United States
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Outros
Publicado em 30/11/2012 EN_US
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Document granting certiorari to Assoc. for Molecular Pathology v. Myriad Genetics, Inc., et al.

Transcript of Oral Arguments for Assoc. Molecular Pathology v. Myriad Genetics, Inc. et al.

Supreme Court of the United States
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Outros
Publicado em 15/04/2013 EN_US
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Transcript of the oral arguments for Association for Molecular Pathology v. Myriad Genetics, Inc. et al.

Decision on Case No. 2010-1405: Association for Molecular Pathology v. Myriad Genetics, Inc., et al.

The United States Court of Appeals for the Federal Circuit
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Outros
Publicado em 29/07/2011 EN_US
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Decision issued by the United States Court of Appeals for the Federal Circuit on Association of Molecular Pathology v. Myriad Genetics, Inc., et al (No. 2010-1406). Opinion for the court was filed by Judge Lourie, with opinions concurring in part filed by Judge Moore and concurring in part and dissenting in part by Judge Bryson.

Amici Brief of Certain Academics in Law, Medicine, Health Policy, and Clinical Genetics in Support of Petitioners

Gold, E. Richard; Evans, James P.; Bubela, Tania; Cook-Deegan, Robert Mullan; Nicol, Dianne
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Outros
Publicado em 13/01/2012 EN_US
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Brief of Amici Curiae ("friend of the court") submitted by certain academics in law, medicine, health policy, and clinical genetics in support of petitioners on petition for a Writ of Certiorari (No. 11-725)

CAFC Decision on Association of Molecular Pathology v. Myriad Genetics, Inc., et al.

United States Court of Appeals for the Federal Circuit
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Outros
Publicado em 16/08/2012 EN_US
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Decision rendered by the United States Court of Appeals for the Federal Circuit on Association of Molecular Pathology v Myriad Genetics, Inc. et al. Opinion for the Court was filed by Judge Lourie, with an opinion concurring in part filed by Judge Moore, and an opinion concurring in part and dissenting in part filed by Judge Bryson.

Lawsuit against Myriad Genetics

Hansen, Christopher A.; Lapidus, Lenora M.; Park, Sandra S.; Ravicher, Daniel B.
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Outros
Publicado em 12/05/2009 EN_US
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Initial complaint filed against Myriad Genetics