Author: "Astrid M. Vicente" / Search Limiters: Peer Reviewed - Searchworks@Jio Institute Digital Library Search Results

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24 results on '"Astrid M. Vicente"'

1. How personalised medicine will transform healthcare by 2030: the ICPerMed vision

Author: Astrid M. Vicente, Wolfgang Ballensiefen, and Jan-Ingvar Jönsson
Subjects: Personalised medicine, ICPerMed, Vision for 2030, Healthcare, Medicine
Abstract: Abstract This commentary presents the vision of the International Consortium for Personalised Medicine (ICPerMed) on how personalised medicine (PM) will lead to the next generation of healthcare by 2030. This vision focuses on five perspectives: individual and public engagement, involvement of health professionals, implementation within healthcare systems, health-related data, and the development of sustainable economic models that allow improved therapy, diagnostic and preventive approaches as new healthcare concepts for the benefit of the public. We further identify four pillars representing transversal issues that are crucial for the successful implementation of PM in all perspectives. The implementation of PM will result in more efficient and equitable healthcare, access to modern healthcare methods, and improved control by individuals of their own health data, as well as economic development in the health sector.
Published: 2020
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2. A Role for Gene-Environment Interactions in Autism Spectrum Disorder Is Supported by Variants in Genes Regulating the Effects of Exposure to Xenobiotics

Author: João Xavier Santos, Célia Rasga, Ana Rita Marques, Hugo Martiniano, Muhammad Asif, Joana Vilela, Guiomar Oliveira, Lisete Sousa, Ana Nunes, and Astrid M. Vicente
Subjects: autism spectrum disorder, blood-brain barrier, detoxification, gene-environment interactions, placenta, xenobiotics exposure, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Heritability estimates support the contribution of genetics and the environment to the etiology of Autism Spectrum Disorder (ASD), but a role for gene-environment interactions is insufficiently explored. Genes involved in detoxification pathways and physiological permeability barriers (e.g., blood-brain barrier, placenta and respiratory airways), which regulate the effects of exposure to xenobiotics during early stages of neurodevelopment when the immature brain is extremely vulnerable, may be particularly relevant in this context. Our objective was to identify genes involved in the regulation of xenobiotic detoxification or the function of physiological barriers (the XenoReg genes) presenting predicted damaging variants in subjects with ASD, and to understand their interaction patterns with ubiquitous xenobiotics previously implicated in this disorder. We defined a panel of 519 XenoReg genes through literature review and database queries. Large ASD datasets were inspected for in silico predicted damaging Single Nucleotide Variants (SNVs) (N = 2,674 subjects) or Copy Number Variants (CNVs) (N = 3,570 subjects) in XenoReg genes. We queried the Comparative Toxicogenomics Database (CTD) to identify interaction pairs between XenoReg genes and xenobiotics. The interrogation of ASD datasets for variants in the XenoReg gene panel identified 77 genes with high evidence for a role in ASD, according to pre-specified prioritization criteria. These include 47 genes encoding detoxification enzymes and 30 genes encoding proteins involved in physiological barrier function, among which 15 are previous reported candidates for ASD. The CTD query revealed 397 gene-environment interaction pairs between these XenoReg genes and 80% (48/60) of the analyzed xenobiotics. The top interacting genes and xenobiotics were, respectively, CYP1A2, ABCB1, ABCG2, GSTM1, and CYP2D6 and benzo-(a)-pyrene, valproic acid, bisphenol A, particulate matter, methylmercury, and perfluorinated compounds. Individuals carrying predicted damaging variants in high evidence XenoReg genes are likely to have less efficient detoxification systems or impaired physiological barriers. They can therefore be particularly susceptible to early life exposure to ubiquitous xenobiotics, which elicit neuropathological mechanisms in the immature brain, such as epigenetic changes, oxidative stress, neuroinflammation, hypoxic damage, and endocrine disruption. As exposure to environmental factors may be mitigated for individuals with risk variants, this work provides new perspectives to personalized prevention and health management policies for ASD.
Published: 2022
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3. Linkage disequilibrium and diversity for three genomic regions in Azoreans and mainland Portuguese

Author: Claudia C. Branco, Paula R. Pacheco, Ester Cabrol, Rita Cabral, Astrid M. Vicente, and Luisa Mota-Vieira
Subjects: linkage disequilibrium, X-chromosome, Y-chromosome, HLA, São Miguel, Azores, Genetics, QH426-470
Abstract: Studies on linkage disequilibrium (LD) across the genome and populations have been used in recent years with the main objective of improving gene mapping of complex traits. Here, we characterize the patterns of genetic diversity of HLA loci and evaluate LD (D') extent in three genomic regions: Xq13.3, NRY and HLA. In addition, we examine the distribution of DXS1225-DXS8082 haplotype diversity in Azoreans and mainland Portuguese. Allele distribution has demonstrated that the São Miguel population is genetically very diverse; haplotype analysis revealed 100% discriminatory power for X- and Y-markers and 94.3% for HLA markers. Standardized multiallelic D' in these three genomic regions shows values lower than 0.33, thereby suggesting there is no extensive LD in the São Miguel population. Data regarding the distribution of DXS1225-DXS8082 haplotypes indicate that there are no significant differences among all the populations studied, (Azorean geographical groups, the Azores archipelago and mainland Portugal). Moreover, in these as well as in other European populations, the most frequent DXS1225-DXS8082 haplotype is 210-219. Even though São Miguel islanders and Azoreans do not constitute isolated populations and show LD for only very short physical distances, certain characteristics, such as the absence of genetic structure, the same environment and the possibility of constructing extensive pedigrees through church and civil records, offer an opportunity for dissecting the genetic background of complex diseases in these populations.
Published: 2009
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4. Dysfunction of the heteromeric Kv7.3/Kv7.5 potassium channel is associated with autism spectrum disorders

Author: Mette eGilling, Hanne Borger Rasmussen, Kirstine eCalloe, Ana Filipa Sequeira, Marta eBaretto, Guiomar eOliveira, Joana eAlmeida, Marlene Briciet Lauritsen, Reinhard eUllmann, Susanne Eriksen Boonen, Karen eBrøndum-Nielsen, Vera M Kalscheuer, Zeynep eTümer, Astrid M. Vicente, Nicole eSchmitt, and Niels eTommerup
Subjects: autism, SNP, translocation, KCNQ3, KCNQ5, KV7.3, Genetics, QH426-470
Abstract: Heterozygous mutations in the KCNQ3 gene on chromosome 8q24 encoding the voltage-gated potassium channel KV7.3 subunit have previously been associated with rolandic epilepsy and idiopathic generalized epilepsy (IGE) including benign neonatal convulsions. We identified a de novo t(3;8)(q21;q24) translocation truncating KCNQ3 in a boy with childhood autism. In addition, we identified a c.1720C>T [p.P574S] nucleotide change in three unrelated individuals with childhood autism and no history of convulsions. This nucleotide change was previously reported in patients with rolandic epilepsy or IGE and has now been annotated as a very rare SNP (rs74582884) in dbSNP. The p.P574S Kv7.3 variant significantly reduced potassium current amplitude in Xenopus laevis oocytes when co-expressed with Kv7.5 but not with Kv7.2 or Kv7.4. The nucleotide change did not affect trafficking of heteromeric mutant Kv7.3/2, Kv7.3/4 or Kv7.3/5 channels in HEK 293 cells or primary rat hippocampal neurons. Our results suggest that dysfunction of the heteromeric Kv7.3/5 channel is implicated in the pathogenesis of some forms of autism spectrum disorders (ASD), epilepsy and possibly other psychiatric disorders and therefore, KCNQ3 and KCNQ5 are suggested as candidate genes for these disorders.
Published: 2013
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5. Efficacy of focused social and communication intervention practices for young children with autism spectrum disorder: A meta-analysis

Author: Clara Fernández-Álvarez, Patricia García-Primo, Célia Rasga, Catia Café, Evald Saemundsen, Álvaro Bejarano-Martín, Manuel Posada, Astrid M. Vicente, Sigrídur Lóa-Jónsdóttir, María Magán-Maganto, and Ricardo Canal-Bedia
Subjects: education.field_of_study, Joint attention, Sociology and Political Science, 05 social sciences, Population, 050301 education, Eye contact, Single-subject design, medicine.disease, Education, Developmental psychology, Nap, Communication Intervention, Autism spectrum disorder, Meta-analysis, Developmental and Educational Psychology, medicine, 0501 psychology and cognitive sciences, education, Psychology, 0503 education, 050104 developmental & child psychology
Abstract: Focused intervention practices (FIPs) are widely used to improve social communication skills, as they are specifically aimed at enhancing skills identified as being problematic in children with autism spectrum disorder ASD, such as imitation, eye contact, gestures, joint attention and play. This meta-analysis was performed to ascertain the overall effectiveness of FIPs in children with ASD 6 years of age and younger. Five electronic searches were conducted, 1828 references were retrieved, and 43 studies 59 outcome measures were included in the meta-analysis. Studies included 785 participants 41.6 months with ASD. The overall socio-communicative effect size for each specific skill imitation, joint attention, and play was calculated using the Hedges’ g (g) for group design studies, and the Nonoverlap of All Pairs (NAP) for single case design studies. Random-effects metaregression models and correlations were also used to assess whether the results were different according to population and intervention characteristics. The impact of possible publication bias was analysed. The results suggest that, whereas FIPs have medium to large positive effects (g = 0.51; NAP = 0.86), those where caregivers or teachers play an active role (g = 0.50; NAP = 0.89) have medium effect sizes. All social and communicative skills outcomes of FIPs have medium effect sizes (Imitation: g = 0.42, NAP = 0.90; Joint attention: g = 0.54, NAP = 0.86; Play: g = 0.47, NAP = 0.81). Effect sizes were greater when participants’ preintervention ages were lower and treatment dosage was higher. When it comes to achieving substantial improvements, factors to be highlighted are the role of caregivers and adaptation of the programme to the characteristics of the child. Implementation of early intervention programmes should be substantiated by a sufficient amount of information about the characteristics of each participant. Professionals should take this information into account in order to select as accurately as possible those procedures that are most effective and feasible.
Published: 2020
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6. Definition of a putative pathological region in PARK2 associated with autism spectrum disorder through in silico analysis of its functional structure

Author: Maria M. Rama, Frederico Duque, Susana Mouga, Cátia Café, Joana Almeida, Bárbara Oliveira, Astrid M. Vicente, Inês C. Conceição, and Guiomar Oliveira
Subjects: Male, 0301 basic medicine, DNA Copy Number Variations, Autism Spectrum Disorder, Ubiquitin-Protein Ligases, In silico, medicine.disease_cause, Copy Number Variants, Parkin, Structure-Activity Relationship, 03 medical and health sciences, 0302 clinical medicine, Ubiquitin, Variant Pathogenicity, Genetics, medicine, Humans, Coding region, Computer Simulation, Copy-number variation, PARK2 gene, Biological Psychiatry, Genetics (clinical), Mutation, Portugal, biology, Parkinson Disease, medicine.disease, Ubiquitin ligase, Psychiatry and Mental health, 030104 developmental biology, Neurodevelopmental Disorders, Autism spectrum disorder, Perturbações do Desenvolvimento Infantil e Saúde Mental, biology.protein, Female, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract: Objective: The PARK2 gene encodes Parkin, a component of a multiprotein E3 ubiquitin ligase complex that targets substrate proteins for proteasomal degradation. PARK2 mutations are frequently associated with Parkinson’s disease, but structural alterations have also been described in patients with neurodevelopmental disorders (NDD), suggesting a pathological effect ubiquitous to neurodevelopmental and neurodegenerative brain processes. The present study aimed to define the critical regions for NDD within PARK2. Materials and methods: To clarify PARK2 involvement in NDDs, we examined the frequency and location of copy number variants (CNVs) identified in patients from our sample and reported in the literature and relevant databases, and compared with control populations. Results: Overall, the frequency of PARK2 CNVs was higher in controls than in NDD cases. However, closer inspection of the CNV location in PARK2 showed that the frequency of CNVs targeting the Parkin C-terminal, corresponding to the ring-between-ring (RBR) domain responsible for Parkin activity, is significantly higher in NDD cases than in controls. In contrast, CNVs targeting the N-terminal of Parkin, including domains that regulate ubiquitination activity, are very common both in cases and in controls. Conclusion: Although PARK2 may be a pathological factor for NDDs, likely not all variants are pathogenic, and a conclusive assessment of PARK2 variant pathogenicity requires an accurate analysis of their location within the coding region and encoded functional domains. Inês C. Conceição was supported by grant SFRH/BPD/74739/2010 from Fundação para a Ciência e Tecnologia (Portugal). info:eu-repo/semantics/publishedVersion
Published: 2017
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7. Identifying disease genes using machine learning and gene functional similarities, assessed through Gene Ontology

Author: Muhammad Asif, Hugo Martiniano, Francisco M. Couto, and Astrid M. Vicente
Subjects: 0301 basic medicine, Candidate gene, Pervasive Developmental Disorders, Source code, Computer science, Autism Spectrum Disorder, Social Sciences, computer.software_genre, Biochemistry, Machine Learning, User-Computer Interface, 0302 clinical medicine, Semantic similarity, Psychology, media_common, Disease gene, Multidisciplinary, Statistics, Genomics, Random forest, Phenotype, Autism spectrum disorder, Area Under Curve, Physical Sciences, Medicine, DECIPHER, Supervised Machine Learning, Research Article, Computer and Information Sciences, Science, Gene prediction, media_common.quotation_subject, Machine learning, behavioral disciplines and activities, Protein–protein interaction, 03 medical and health sciences, Artificial Intelligence, Support Vector Machines, Classifier (linguistics), mental disorders, medicine, Genetics, Humans, Gene Prediction, Protein Interactions, Gene, business.industry, Biology and Life Sciences, Computational Biology, Proteins, medicine.disease, Genome Analysis, Support vector machine, 030104 developmental biology, Gene Ontology, ROC Curve, Protein-Protein Interactions, Attention Deficit Disorder with Hyperactivity, Developmental Psychology, Genetics of Disease, Autism, Similarity Measures, Artificial intelligence, business, computer, Classifier (UML), 030217 neurology & neurosurgery, Mathematics
Abstract: Identifying disease genes from a vast amount of genetic data is one of the most challenging tasks in the post-genomic era. Also, complex diseases present highly heterogeneous genotype, which difficult biological marker identification. Machine learning methods are widely used to identify these markers, but their performance is highly dependent upon the size and quality of available data.In this study, we demonstrated that machine learning classifiers trained on gene functional similarities, using Gene Ontology (GO), can improve the identification of genes involved in complex diseases. For this purpose, we developed a supervised machine learning methodology to predict complex disease genes. The proposed pipeline was assessed using Autism Spectrum Disorder (ASD) candidate genes. A quantitative measure of gene functional similarities was obtained by employing different semantic similarity measures. To infer the hidden functional similarities between ASD genes, various types of machine learning classifiers were built on quantitative semantic similarity matrices of ASD and non-ASD genes. The classifiers trained and tested on ASD and non-ASD gene functional similarities outperformed previously reported ASD classifiers. For example, a Random Forest (RF) classifier achieved an AUC of 0. 80 for predicting new ASD genes, which was higher than the reported classifier (0.73). Additionally, this classifier was able to predict 73 novel ASD candidate genes that were were enriched for core ASD phenotypes, such as autism and obsessive-compulsive behavior. In addition, predicted genes were also enriched for ASD co-occurring conditions, including Attention Deficit Hyperactivity Disorder (ADHD).We also developed a KNIME workflow with the proposed methodology which allows users to configure and execute it without requiring machine learning and programming skills. Machine learning is an effective and reliable technique to decipher ASD mechanism by identifying novel disease genes, but this study further demonstrated that their performance can be improved by incorporating a quantitative measure of gene functional similarities. Source code and the workflow of the proposed methodology are available at https://github.com/Muh-Asif/ASD-genes-prediction.
Published: 2018

8. Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders

Author: Joana Almeida, Christian R. Marshall, Hakon Hakonarson, Bárbara Oliveira, Anthony J. Griswold, Jacob A. S. Vorstman, Bhooma Thiruvahindrapuram, Suma Jacob, Judith Conroy, Alistair T. Pagnamenta, Christelle Cabrol, Jeremy R. Parr, Daniel H. Geschwind, Nancy J. Minshew, Xiao Xu, Richard Anney, Sven Bölte, Zhuozhi Wang, Emily L. Crawford, Elsa Delaby, Margaret A. Pericak-Vance, Joachim Hallmayer, Jonathan L. Haines, Dalila Pinto, Susana Mouga, Alexander Kolevzon, Elena Bacchelli, Frederico Duque, Bernie Devlin, Latha Soorya, Cátia Café, Kirsty Wing, Jennifer K. Lowe, Ana Tryfon, Stephen J. Guter, Geraldine Dawson, Tiago R. Magalhaes, Anthony J. Bailey, Michael Gill, Peter Szatmari, Steven Gallinger, Marion Pilorge, James S. Sutcliffe, Bridget A. Fernandez, Herman van Engeland, Catalina Betancur, Guiomar Oliveira, Andrew Green, Eftichia Duketis, Bernadette Rogé, Ann Le Couteur, Evdokia Anagnostou, Michelle Cotterchio, Daniele Merico, Giovanna Pellecchia, Jonathan Green, Regina Regan, Jillian P. Casey, Guiqing Cai, Gerard D. Schellenberg, Jennifer L. Howe, Elena Maestrini, Andrew D. Paterson, L. Alison McInnes, Patrick Bolton, Edwin H. Cook, Richard Delorme, Lambertus Klei, Thomas Bourgeron, Gillian Baird, Christine M. Freitag, Beth A. Dombroski, Andreas G. Chiocchetti, Sabine M. Klauck, Susan E. Folstein, Mafalda Barbosa, Anthony P. Monaco, Marion Leboyer, Nadia Bolshakova, Fritz Poustka, Richard Holt, Kerstin Wittemeyer, Wendy Roberts, Lonnie Zwaigenbaum, Louise Gallagher, Susan G. McGrew, Joseph D. Buxbaum, Graham Casey, Simon Wallace, Catherine Lord, Sean Brennan, Robert Ziman, Alison K. Merikangas, John I. Nurnberger, Christopher Gillberg, Ellen M. Wijsman, Astrid M. Vicente, Inȇs C. Conceição, Sean Ennis, Patricia Jiménez González, Hilary Coon, Raphael Bernier, John R. Gilbert, Ann P. Thompson, Susanne Thomson, Agatino Battaglia, Maretha de Jonge, Michael L. Cuccaro, Catarina Correia, Veronica J. Vieland, Stephen W. Scherer, Pauline Chaste, Departments of Psychiatry, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Seaver Autism Center-, The Mindich Child Health & Development Institute, Department of Psychiatry, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Seaver Autism Center for Research and Treatment, Friedman Brain Institute, The Mindich Child Health and Development Institute, The Icahn Institute for Genomics and Multiscale Biology, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Trinity College Dublin-St. James's Hospital, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), McLaughlin Centre, University of Toronto, BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Department of Neurology, University of California [Los Angeles] (UCLA), University of California-University of California-David Geffen School of Medicine [Los Angeles], University of California-University of California, Fisico-Quimica Biologica, Universidade Federal do Rio de Janeiro (UFRJ), John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Department of Pathology, Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Prevention & Cancer Control, Cancer Care Ontario, Department of Preventive Medicine, University of Southern California (USC), Department of Pediatrics, University of Alberta, School of Education, University of Birmingham [Birmingham], University of Oxford [Oxford]-Warneford Hospital, Octogone Unité de Recherche Interdisciplinaire (Octogone), Université Toulouse - Jean Jaurès (UT2J), Autism Research Unit, The Hospital for sick children [Toronto] (SickKids)-University of Toronto, Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Institute for Biomedical Imaging and Life Science, University of Coimbra [Portugal] (UC), Vanderbilt University [Nashville], Center for Autism and the Developing Brain (CADB), Weill Medical College of Cornell University [New York], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institute of Health and Society, Newcastle University [Newcastle], Department of Child and Adolescent Psychiatry, Newcastle University [Newcastle]-Institute of Health & Society (Child & Adolescent Psychiatry), Child Developmental and Behavioral Unit, Hospital Nacional de Niños Dr Sáenz Herrera, Institute for Juvenile Research-University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Manchester Academic Health Sciences Centre, Gillberg Neuropsychiatry Centre [Göteborg, Sueden], Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg (GU), Institute of Child Health, University College of London [London] (UCL), Memorial University of Newfoundland [St. John's], Disciplines of Genetics and Medicine, Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Institute of Psychiatry, King‘s College London, Institute of psychiatry, University of Washington [Seattle], Paediatric Neurodisability, King‘s College London-King's Health Partners, MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, University of British Columbia (UBC), Bloorview Research Institute, Division of Medical Genetics [Seattle], Departments of Biostatistics and Medicine, Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, Institute of Neuroscience [Newcastle] (ION), Institutes of Neuroscience and Health and Society, Indiana University School of Medicine, Indiana University System-Indiana University System, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Utah Autism Research Program, University of Utah Psychiatry Department, University of Miami School of Medicine, Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris [Pisa], Department of Psychiatry and Behavioral Sciences [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford School of Medicine [Stanford], Institute for Juvenile Research, University of Illinois [Chicago] (UIC), Department of Neuroscience, Main funders of the Autism Genome Project: Autism Speaks (USA), the Health Research Board (Ireland, AUT/2006/1, AUT/2006/2, PD/2006/48), the Medical Research Council (UK), the Hilibrand Foundation (USA), Genome Canada, the Ontario Genomics Institute, and the Canadian Institutes of Health Research (CIHR), Autism Genome Project Consortium, Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Oxford, University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], University of California (UC)-University of California (UC), University of Pennsylvania, University of Oxford-Warneford Hospital, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP ), Betancur, Catalina, Instituto Nacional de Saude Dr Ricardo Jorge, Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement (LAMBE - UMR 8587), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Università di Bologna [Bologna] (UNIBO), Mount Sinai Hospital (MSH), University of Toronto-The Hospital for Sick Children, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Gillberg Neuropsychiatry Centre, University of Gothenburg (GU), Stanford University Medical School, Stanford University School of Medicine [Stanford], Stanford University [Stanford], Université de Toulouse (UT)-Université de Toulouse (UT), Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, Thiruvahindrapuram B, Xu X, Ziman R, Wang Z, Vorstman JA, Thompson A, Regan R, Pilorge M, Pellecchia G, Pagnamenta AT, Oliveira B, Marshall CR, Magalhaes TR, Lowe JK, Howe JL, Griswold AJ, Gilbert J, Duketis E, Dombroski BA, De Jonge MV, Cuccaro M, Crawford EL, Correia CT, Conroy J, Conceição IC, Chiocchetti AG, Casey JP, Cai G, Cabrol C, Bolshakova N, Bacchelli E, Anney R, Gallinger S, Cotterchio M, Casey G, Zwaigenbaum L, Wittemeyer K, Wing K, Wallace S, van Engeland H, Tryfon A, Thomson S, Soorya L, Rogé B, Roberts W, Poustka F, Mouga S, Minshew N, McInnes LA, McGrew SG, Lord C, Leboyer M, Le Couteur AS, Kolevzon A, Jiménez González P, Jacob S, Holt R, Guter S, Green J, Green A, Gillberg C, Fernandez BA, Duque F, Delorme R, Dawson G, Chaste P, Café C, Brennan S, Bourgeron T, Bolton PF, Bölte S, Bernier R, Baird G, Bailey AJ, Anagnostou E, Almeida J, Wijsman EM, Vieland VJ, Vicente AM, Schellenberg GD, Pericak-Vance M, Paterson AD, Parr JR, Oliveira G, Nurnberger JI, Monaco AP, Maestrini E, Klauck SM, Hakonarson H, Haines JL, Geschwind DH, Freitag CM, Folstein SE, Ennis S, Coon H, Battaglia A, Szatmari P, Sutcliffe JS, Hallmayer J, Gill M, Cook EH, Buxbaum JD, Devlin B, Gallagher L, Betancur C, and Scherer SW.
Subjects: Male, INTELLECTUAL DISABILITY, pathways, Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Bioinformatics, DUPLICATIONS, Intellectual disability, Gene Regulatory Networks, Genetics(clinical), Copy-number variation, 10. No inequality, Child, GDI1, Genetics (clinical), Sequence Deletion, COPY NUMBER VARIANTS, Genetics, gene networks, Copy Number Variation, 3. Good health, Pedigree, Fragile X syndrome, Multigene Family, Female, Metabolic Networks and Pathways, de novo, DNA Copy Number Variations, autism, Biology, rare CNV, PHENOTYPE ONTOLOGY, Article, Structural variation, mental disorders, medicine, Humans, ddc:610, FRAGILE-X-SYNDROME, GENOME-WIDE ASSOCIATION, Gene, [SDV.GEN]Life Sciences [q-bio]/Genetics, HDAC4, SETD5, medicine.disease, CHD2, inherited, STRUCTURAL VARIATION, DELETIONS, DE-NOVO MUTATIONS, Child Development Disorders, Pervasive, Autism
Abstract: International audience; Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
Published: 2014
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9. Association of a Genetic Variant in the ALOX5AP with Higher Risk of Ischemic Stroke: A Case-Control, Meta-Analysis and Functional Study

Author: Joan Martí-Fàbregas, Maite Mendioroz, Helena Manso, José Alvarez-Sabín, Liliana O. Gouveia, Tiago Krug, A. Del Rio-Espinola, Israel Fernandez-Cadenas, Natalia Corbeto, Sofia A. Oliveira, M. Freijo, Marta Rubiera, José M. Ferro, João Sobral, Jèssica Fernández-Morales, Joan Montaner, Astrid M. Vicente, Sophie Domingues-Montanari, Victor Obach, J. Serena, and Marc Ribó
Subjects: business.industry, Haplotype, Ischemia, Phosphodiesterase, Single-nucleotide polymorphism, medicine.disease, Bioinformatics, Neurology, Meta-analysis, Genotype, medicine, Neurology (clinical), Allele, Cardiology and Cardiovascular Medicine, business, Stroke
Abstract: Background: Variants in the 5-lipoxygenase-activating protein (ALOX5AP) and phosphodiesterase 4D (PDE4D) genes have first been associated with ischemic stroke (IS) through whole-genome linkage screens. However, association studies obtained conflicting results. We aimed to investigate the contribution of selected single nucleotide polymorphisms (SNPs) in these genes for the first time in a large Iberian population. Methods: A case-control design was used to analyze one SNP in ALOX5AP and five SNPs in PDE4D in a total of 1,092 IS patients and 781 healthy controls of two different subsets from Spain and Portugal. The analysis was adjusted for confounding variables and the results were integrated in a meta-analysis of all case-control studies. In addition, ALOX5AP gene expression levels were determined in controls and IS cases. Results: A first meta-analysis of both subsets showed that the T allele of the SG13S114 SNP in ALOX5AP was a risk factor for IS after Bonferroni correction [OR = 1.22 (1.06–1.40); p = 0.006]. A second meta-analysis of white populations confirmed these results [OR = 1.18 (1.07–1.31); p = 0.001]. ALOX5AP gene expression analysis in a subset of controls and cases revealed that the SG13S114 genotypes modulate mRNA levels of ALOX5AP (p = 0.001) and mRNA levels were higher in IS cases (2.8 ± 2.4%) than in controls (1.4 ± 1.3%; p = 0.003). No association of the variants in PDE4D with IS was observed in our study. Conclusions: The ALOX5AP SG13S114 variant is an independent risk factor for IS in the Iberian population and is associated with ALOX5AP expression levels. The role of this gene in stroke merits further investigation.
Published: 2010
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10. A 3.2 Mb deletion on 18q12 in a patient with childhood autism and high-grade myopia

Author: Paal Skyt Andersen, Reinhard Ullmann, Christina Cintin, Rodney M. J. Cotterill, Ole Mors, Astrid M. Vicente, Niels Tommerup, Marlene Briciet Lauritsen, Iben Bache, Claes Lundsteen, Karen Friis Henriksen, Thomas Rosenberg, Zeynep Tümer, Karen Brøndum-Nielsen, Guiomar Oliveira, Hans Eiberg, Morten Møller, Hans-Hilger Ropers, and Mette Gilling
Subjects: Adult, Perturbação Autística, Autism, Miopia, Translocation, Chromosomal translocation, Epigenetics of autism, Array CGH, Biology, behavioral disciplines and activities, Deletion, 03 medical and health sciences, 0302 clinical medicine, Chromosome 18, mental disorders, Genetic model, Myopia, Genetics, medicine, Humans, Heritability of autism, Autistic Disorder, Child, In Situ Hybridization, Genetics (clinical), Sequence Deletion, 030304 developmental biology, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, medicine.disease, Developmental disorder, Cromossoma Humano Par 18, Perturbações do Desenvolvimento Infantil e Saúde Mental, Female, Chromosomes, Human, Pair 18, Haploinsufficiency, 030217 neurology & neurosurgery
Abstract: Udgivelsesdato: 2008-Mar Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with unknown aetiology. Even though ASDs are suggested to be among the most heritable complex disorders, only a few reproducible mutations leading to susceptibility for ASD have been identified. In an attempt to identify ASD susceptibility genes through chromosome rearrangements, we investigated a female patient with childhood autism and high-grade myopia, and an apparently balanced de novo translocation, t(5;18)(q34;q12.2). Further analyses revealed a 3.2 Mb deletion encompassing 17 genes at the 18q break point and an additional deletion of 1.27 Mb containing two genes on chromosome 4q35. Q-PCR analysis of 14 of the 17 genes deleted on chromosome 18 showed that 11 of these genes were expressed in the brain, suggesting that haploinsufficiency of one or more genes may have contributed to the childhood autism phenotype of the patient. Identification of multiple genetic changes in this patient with childhood autism agrees with the most frequently suggested genetic model of ASDs as complex, polygenic disorders.
Published: 2008
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11. Pharmacogenetics of risperidone response and induced side effects

Author: Catarina Correia and Astrid M. Vicente
Subjects: Pharmacology, Drug, Risperidone, business.industry, medicine.drug_class, medicine.medical_treatment, media_common.quotation_subject, Atypical antipsychotic, General Medicine, Extrapyramidal symptoms, Pharmacodynamics, Molecular Medicine, Medicine, medicine.symptom, business, Antipsychotic, Adverse effect, Pharmacogenetics, medicine.drug, media_common
Abstract: Risperidone is an atypical antipsychotic that has been effectively used to treat several psychiatric diseases. Atypical antipsychotics present some advantages over conventional antipsychotics, primarily because they offer effective treatment alternatives that are relatively free of extrapyramidal symptoms. However, as with all antipsychotics, there are wide individual differences in response to risperidone, both regarding therapeutic effects and adverse effects, imposing some limitations with respect to the therapeutic use of the drug. Genetic factors are thought to play an important role in determining the variability to drug response. A growing number of studies are investigating how genetic polymorphisms of enzymes involved in drug metabolism or of receptors targeted by antipsychotic agents influence drug treatment of several neuropsychiatric diseases. In this article we will review the genetic variability in both the pharmacokinetics of risperidone action and in pharmacodynamic structures mediating risperidone effects, as well as the pharmacogenetic studies performed for these genes.
Published: 2007
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12. Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levels

Author: Guiomar Oliveira, Assunção Ataíde, C.C. Marques, Ana M. Coutinho, Teresa S. Miguel, Jason H. Moore, Teresa Morgadinho, Inês Sousa, Catarina Correia, Astrid M. Vicente, Madalena Martins, and Celeste Bento
Subjects: Blood Platelets, Male, Serotonin, Candidate gene, Adolescent, Biology, Linkage Disequilibrium, 03 medical and health sciences, 0302 clinical medicine, Neurodevelopmental disorder, Genetics, medicine, Humans, Genetic Predisposition to Disease, Heritability of autism, Autistic Disorder, Child, Genetics (clinical), 030304 developmental biology, Serotonin Plasma Membrane Transport Proteins, 0303 health sciences, TPH1, Haplotype, Integrin beta3, Epistasis, Genetic, Transmission disequilibrium test, medicine.disease, Developmental disorder, Haplotypes, Child, Preschool, Perturbações do Desenvolvimento Infantil e Saúde Mental, Autism, Female, 030217 neurology & neurosurgery
Abstract: Autism is a neurodevelopmental disorder of unclear etiology. The consistent finding of platelet hyperserotonemia in a proportion of patients and its heritability within affected families suggest that genes involved in the serotonin system play a role in this disorder. The role in autism etiology of seven candidate genes in the serotonin metabolic and neurotransmission pathways and mapping to autism linkage regions (SLC6A4, HTR1A, HTR1D, HTR2A, HTR5A, TPH1 and ITGB3) was analyzed in a sample of 186 nuclear families. The impact of interactions among these genes in autism was assessed using the multifactor-dimensionality reduction (MDR) method in 186 patients and 181 controls. We further evaluated whether the effect of specific gene variants or gene interactions associated with autism etiology might be mediated by their influence on serotonin levels, using the quantitative transmission disequilibrium test (QTDT) and the restricted partition method (RPM), in a sample of 109 autistic children. We report a significant main effect of the HTR5A gene in autism (P = 0.0088), and a significant three-locus model comprising a synergistic interaction between the ITGB3 and SLC6A4 genes with an additive effect of HTR5A (P < 0.0010). In addition to the previously reported contribution of SLC6A4, we found significant associations of ITGB3 haplotypes with serotonin level distribution (P = 0.0163). The most significant models contributing to serotonin distribution were found for interactions between TPH1 rs4537731 and SLC6A4 haplotypes (P = 0.002) and between HTR1D rs6300 and SLC6A4 haplotypes (P = 0.013). In addition to the significant independent effects, evidence for interaction between SLC6A4 and ITGB3 markers was also found. The overall results implicate SLC6A4 and ITGB3 gene interactions in autism etiology and in serotonin level determination, providing evidence for a common underlying genetic mechanism and a molecular explanation for the association of platelet hyperserotonemia with autism.
Published: 2007
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13. Brief Report: High Frequency of Biochemical Markers for Mitochondrial Dysfunction in Autism: No Association with the Mitochondrial Aspartate/Glutamate Carrier SLC25A12 Gene

Author: Luís Borges, Assunção Ataíde, Joana Almeida, Astrid M. Vicente, Ana M. Coutinho, C.C. Marques, Manuela Grazina, Catarina R. Oliveira, Luísa Diogo, Guiomar Oliveira, Teresa S. Miguel, and Catarina Correia
Subjects: medicine.medical_specialty, Mitochondrial Diseases, DNA Mutational Analysis, Gene Expression, Glutamic Acid, Mitochondrion, DNA, Mitochondrial, Mitochondrial Membrane Transport Proteins, Genetic determinism, Mitochondrial Proteins, Gene Frequency, Internal medicine, Pyruvic Acid, Developmental and Educational Psychology, medicine, Glutamate aspartate transporter, Humans, Lactic Acid, Autistic Disorder, Gene, DNA Primers, Aspartic Acid, biology, Metabolic disorder, Glutamate receptor, Chromosome Mapping, Membrane Transport Proteins, medicine.disease, Developmental disorder, Endocrinology, Haplotypes, biology.protein, Autism, Psychology
Abstract: In the present study we confirm the previously reported high frequency of biochemical markers of mitochondrial dysfunction, namely hyperlactacidemia and increased lactate/pyruvate ratio, in a significant fraction of 210 autistic patients. We further examine the involvement of the mitochondrial aspartate/glutamate carrier gene (SLC25A12) in mitochondrial dysfunction associated with autism. We found no evidence of association of the SLC25A12 gene with lactate and lactate/pyruvate distributions or with autism in 241 nuclear families with one affected individual. We conclude that while mitochondrial dysfunction may be one of the most common medical conditions associated with autism, variation at the SLC25A12 gene does not explain the high frequency of mitochondrial dysfunction markers and is not associated with autism in this sample of autistic patients.
Published: 2006
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14. Autoantibody repertoires to brain tissue in autism nuclear families

Author: Ana M. Coutinho, Constantin Fesel, Susana C Silva, Astrid M. Vicente, C.C. Marques, Celeste Bento, Guiomar Oliveira, Marta Barreto, Assunção Ataíde, Luís Borges, Catarina Correia, and Teresa S. Miguel
Subjects: Male, Adolescent, Blotting, Western, Immunology, medicine.disease_cause, Neuroprotection, Nuclear Family, Autoimmunity, Pathogenesis, Immune system, Antigen, medicine, Humans, Immunology and Allergy, Autistic Disorder, Child, Autoantibodies, biology, Autoantibody, Brain, Myelin Basic Protein, medicine.disease, Myelin basic protein, Neurology, Child, Preschool, biology.protein, Autism, Female, Neurology (clinical), Neuroscience
Abstract: The hypothesis of an immune dysfunction in autism spectrum disorders has previously been put forward without, however, compelling evidence of a direct relation to its etiology or pathogenesis. To further understand if autoimmunity could play a significant role in autism, we analyzed autoantibody repertoires to brain tissue extract in the plasma of 171 autism children, their parents, and 54 controls, by quantitative immunoblotting. Multiparametric analysis revealed significant differences between patients and controls, and showed that one single reactivity in Section 32 of the blot had the most power to discriminate between these samples. Family correlation coefficients and heritability estimates did not provide any evidence that this reactivity was genetically determined. While the molecular weight of the target protein suggested that it might be an isoform of Myelin Basic Protein (MBP), inhibition assays with human MBP argued against this hypothesis. The study evidences the widespread occurrence of autoreactivities to brain tissue in autism patients, which may represent the immune system's neuroprotective response to a previous brain injury occurred during neurodevelopment. The molecular identification of the target protein in Section 32 will contribute to the understanding of the role of immune responses against brain antigens in autistic patients.
Published: 2004
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15. Evidence for epistatic gene interactions between growth factor genes in stroke outcome

Author: Helena Manso, Gisela Gaspar, José M. Ferro, João Sobral, Sofia A. Oliveira, Tiago Krug, Isabel Albergaria, and Astrid M. Vicente
Subjects: Oncology, medicine.medical_specialty, Angiogenesis, business.industry, Growth factor, medicine.medical_treatment, Odds ratio, Fibroblast growth factor, medicine.disease, Vascular endothelial growth factor A, Neurology, Neurotrophic factors, Internal medicine, medicine, Neurology (clinical), business, Stroke recovery, Stroke, Neuroscience
Abstract: Background and purpose: Growth factors are thought to modulate neurological function in stroke recovery through effects in angiogenesis, neurogenesis, and neuroprotection. Methods: We tested the association of variants in the brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) genes, and epistatic interactions between them, with functional outcome in a sample of 546 stroke patients. Results: While none of the tested genes was independently associated with stroke outcome, two significant gene–gene interaction models were identified. One model combined one BDNF and three FGF2 markers, with a global odds ratio (OR) (95% confidence interval [CI]) of 4.15 [2.86–6.04]. The second model included one FGF2 and two VEGFA markers with a global OR [95% CI] = 2.54 [1.76–3.67]. Conclusions: The results provide evidence for gene interactions in stroke outcome, highlighting the complexity of the recovery mechanisms after a stroke event.
Published: 2012
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16. Subject Index Vol. 29, 2010

Author: Christopher F. Bladin, D. Dormont, Masafumi Harada, Astrid M. Vicente, Kenneth Butcher, Delphine Michel-Monigadon, Kristina Szabo, Sofia A. Oliveira, Marta Rubiera, Heinz G. Endres, Jeroen Hendrikse, Sophie Domingues-Montanari, Klaus Berger, S. Crozier, Marc Ribó, Gerhart Tepohl, Natalia Corbeto, Marimar Freijo, Christophe Bonny, Joan Martí-Fàbregas, Christopher R Levi, A. Drier, K.M. Kasius, Jens-Rainer Allenberg, Nikolai Steffenhagen, G.J.E. Rinkel, Jessica Fernández-Morales, Joan Montaner, C. van Heugten, Willem P.Th.M. Mali, Bruce Ovbiagele, Imanuel Dzialowski, Dirk Sander, Naomi Morita, S. Deltour, Ryuuji Kaji, Junichiro Satomi, Maite Mendioroz, Georg Bohner, Joaquín Serena, Angelika Alonso, Lorenz Hirt, M. Coudert, Shelagh B. Coutts, Hiromu Nishitani, C.J.M. Frijns, Stephen M. Davis, Jochen B. Fiebach, José Alvarez-Sabín, P. Renou, D. Galanaud, Kotaro Asanuma, Israel Fernandez-Cadenas, Masaaki Uno, Roman L. Haberl, Geoffrey A. Donnan, A. Algra, Soren Christensen, Stefano Ricci, Markus Schwertfeger, Sarah J. Foster, P. Alan Barber, Curt Diehm, Ina Burghaus, Helena Manso, Saskia H. Meves, Patricia Desmond, David Pittrow, Michael G. Hennerici, José M. Ferro, Y. Samson, T. Tourdias, Andrew M. Demchuk, Meng Lee, Victor Obach, Alberto del Rio-Espinola, Frans L. Moll, Lisa M. Jongen, Christine O'Reilly, Shinji Nagahiro, H. Bart van der Worp, João Sobral, Volker Puetz, M.W.M. Post, Bruce C.V. Campbell, Tiago Krug, M.J.E. van Zandvoort, I. Sibon, Stefan H. Kreisel, C. Rosso, J.M.A. Visser-Meily, Harald Darius, Liliana Gouveia, P.E.C.A. Passier, F. Rouanet, Michael D. Hill, Yuishin Izumi, Mark W Parsons, and Hans-Joachim Trampisch
Subjects: Index (economics), Neurology, business.industry, Statistics, Medicine, Subject (documents), Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Published: 2010
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17. Analysis of the linkage disequilibrium extension in the Azores Islands (Portugal)

Author: M. São Bento, Ester Cabrol, Astrid M. Vicente, Cidália T Gomes, Claudia C. Branco, Luisa Mota-Vieira, Paula Pacheco, and Rita Cabral
Subjects: Disease gene, Genetics, Linkage disequilibrium, education.field_of_study, Genetic distance, Evolutionary biology, Population, Pedigree chart, Mainland, Biology, education, Pathology and Forensic Medicine
Abstract: The design of genetic studies of complex diseases is dependent on the extension and distribution of linkage disequilibrium (LD) across the genome and populations. Here, we characterize the LD extension in the Azores (Western, Central and Eastern islands groups) and mainland Portugal populations. LD was evaluated in three chromosomic regions: the Xq13.3, the Y-chromosome and the HLA (6p21) for the Azorean population. The results obtained in the Western group for the Xq13.3 markers provide significant evidence of LD in 10 comparisons, after correction. In the Sao Miguel island population, the assessment of LD for HLA demonstrated a total of 13 out of 36 pairs with significant LD, with the largest genetic distance (2.5Mb) between HLA-DRB1 and D6S265. The pairwise association between Y-markers in the Azorean population revealed 46% pairs with significant LD. In addition, D ′ analysis indicates that the Western group presents higher values when compared with the Central and Eastern groups. Taken together, the data show that the Azorean population presents a lower D ′ (0.142) compared with mainland Portugal (0.226). Although, both populations do not show extensive LD, the easy reconstruction of large pedigrees in the Azorean population is a valuable resource for the fine mapping of disease genes.
Published: 2008
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18. The Portuguese genetic background in analysis: São Miguel Island (Azores) versus mainland Portugal

Author: Claudia C. Branco, Luisa Mota-Vieira, Astrid M. Vicente, Rita Cabral, and Paula Pacheco
Subjects: Mainland China, Genetic diversity, education.field_of_study, Ecology, Population, Population genetics, Genetic relationship, Pathology and Forensic Medicine, Geography, parasitic diseases, Genetics, Mainland, education, human activities, Inbreeding, Allele frequency
Abstract: To study the genetic diversity of Sao Miguel's population we compared 21 microsatellite loci in 204 individuals from Sao Miguel island and 103 individuals from mainland Portugal. The results show that Sao Miguel and mainland Portugal populations have an average gene diversity of 0.767 and 0.765, respectively. TPOX and D17S976 markers have the lowest (∼0.6) and highest (∼0.9) values, respectively, of gene diversity for both populations. Allele frequencies of all markers are comparable to other European populations. This result is corroborated by the genetic relationship analysis based on the NJ tree and principal component, where Sao Miguel, and probably, Azores is closely related to mainland Portugal. The comparison of F IS values for the mainland (0.0326) and the Sao Miguel (0.0111) samples suggests higher inbreeding in the mainland. Overall, the data suggests that Sao Miguel population does not show population structure and is behaving as an outbred population with high genetic diversity. Taken together, the data complements the settlement history of the Sao Miguel island and of the Azorean population, and will be crucial to predict and explain genotypes implicated in genetic diseases in the Azorean population.
Published: 2008
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19. Study of the genetic relationship and diversity patterns in the Azores based on 15 STR markers

Author: Cidália T Gomes, Rita Cabral, Claudia C. Branco, Luisa Mota-Vieira, M. São Bento, Astrid M. Vicente, and Paula Pacheco
Subjects: education.field_of_study, Genetic diversity, geography, geography.geographical_feature_category, Population, Dendrogram, Population genetics, Genetic relationship, Pathology and Forensic Medicine, Evolutionary biology, Genetic variation, Archipelago, Genetics, Mainland, education
Abstract: The Azores, the largest Portuguese archipelago, is composed of nine islands unevenly distributed by three groups: the Eastern group (Sao Miguel and Santa Maria), the Central (Terceira, Pico, Faial, Sao Jorge and Graciosa) and the Western group (Flores and Corvo). Here, we describe the genetic diversity patterns for each Azorean island and their genetic relationship based on a total of 554 samples. Genotyping was carried out by the multiplex STR system PowerPlex ® 16 (Promega). The results demonstrate that the average gene diversity values vary between 0.768 and 0.797 for Corvo and Terceira, respectively. The comparison of these data with mainland Portugal (0.765) reveals higher values for the Azorean islands. The dendrogram shows that the most distantly apart are Flores and Corvo; however, there is no genetic differentiation between all islands. Moreover, we observe a clustering of the island's populations by their geographical and socio-cultural proximity. On the other hand, historical records mention a differential settlement between islands. The results show that, nowadays, there are no regional genetic differences in the archipelago due to internal migration. Taken together, the knowledge here obtained will provide insights about the allelic structure of health-related genetic variation in the Azorean population.
Published: 2008
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20. Protein interaction networks reveal novel autism risk genes within GWAS statistical noise

Author: Catarina Correia, Guiomar Oliveira, and Astrid M. Vicente
Subjects: Proteomics, Candidate gene, Cytoskeleton organization, Autism, Gene regulatory network, lcsh:Medicine, Genome-wide association study, Biology, Saúde Pública, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Mental Health and Psychiatry, mental disorders, medicine, Genome-Wide Association Studies, Genetics, Medicine and Health Sciences, Humans, Gene Regulatory Networks, Genetic Predisposition to Disease, Protein Interaction Maps, Autistic Disorder, Protein Interactions, lcsh:Science, 030304 developmental biology, Genetic association, 0303 health sciences, Multidisciplinary, Models, Statistical, Portugal, Systems Biology, lcsh:R, Biology and Life Sciences, Proteins, Computational Biology, Genome project, Genomics, medicine.disease, Genome Analysis, Autism spectrum disorder, Genetics of Disease, Perturbações do Desenvolvimento Infantil e Saúde Mental, lcsh:Q, 030217 neurology & neurosurgery, Research Article, Genome-Wide Association Study
Abstract: Genome-wide association studies (GWAS) for Autism Spectrum Disorder (ASD) thus far met limited success in the identification of common risk variants, consistent with the notion that variants with small individual effects cannot be detected individually in single SNP analysis. To further capture disease risk gene information from ASD association studies, we applied a network-based strategy to the Autism Genome Project (AGP) and the Autism Genetics Resource Exchange GWAS datasets, combining family-based association data with Human Protein-Protein interaction (PPI) data. Our analysis showed that autism-associated proteins at higher than conventional levels of significance (P
Published: 2014

21. NCAM and schizophrenia: genetic studies

Author: Anne S. Bassett, Fabio Macciardi, G Bean, M. Verga, William G. Honer, J.L. Kennedy, and Astrid M. Vicente
Subjects: Adult, Male, Genetic Linkage, Haplotype, Epigenetics of schizophrenia, Disease, medicine.disease, Article, Cellular and Molecular Neuroscience, Psychiatry and Mental health, nervous system, Genetic linkage, Schizophrenia, mental disorders, Synaptic plasticity, medicine, Humans, Female, Neural cell adhesion molecule, Psychology, Neural Cell Adhesion Molecules, Molecular Biology, Gene, Neuroscience
Abstract: The hypothesis of a neurodevelopmental dysfunction being involved in the etiology of schizophrenia is suggested by the observation of morphological alterations in the brains of schizophrenia patients. These alterations may be caused by defects in neural cell differentiation or migration, which could lead to disrupted neuronal circuitry and to the schizophrenia symptomatology. The neural cell adhesion molecule (NCAM) plays a major role in cell migration and axon outgrowth, and is involved in synaptic plasticity mechanisms implicated in adult cognitive functions. Altered levels of the NCAM polysialylated form, PSA-NCAM, in the brain of schizophrenia patients have been reported, and are supportive of a role for this molecule in the disorder. To investigate the possible involvement of the NCAM gene in schizophrenia, we conducted a comprehensive genetic study, which included linkage analysis and an association study employing the Haplotype Relative Risk (HRR) design in nuclear families. Our results indicate that structural alterations in the NCAM gene are unlikely to play a major role in schizophrenia, although a function for the NCAM molecule in the etiology of the disease remains an intriguing hypothesis.
Published: 1997
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22. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Author: Veronica J. Vieland, Stephen W. Scherer, Alison K. Merikangas, Naisha Shah, Edwin H. Cook, William M. McMahon, Kirsty Wing, Sabata C. Lund, Jacob A. S. Vorstman, Judith Conroy, Sabine M. Klauck, John B. Vincent, Astrid M. Vicente, Carine Mantoulan, Barbara Parrini, Jeremy R. Parr, Herman van Engeland, Jane McGrath, Guiomar Oliveira, Jonathan Green, James S. Sutcliffe, Peter Szatmari, Ann Le Couteur, Katerina Papanikolaou, Joseph Piven, Andrew Pickles, Gillian Baird, Inês Sousa, Gerard D. Schellenberg, Catarina Correia, Bennett L. Leventhal, Helen McConachie, Joseph T. Glessner, Fritz Poustka, Alistair T. Pagnamenta, Marion Leboyer, Nuala Sykes, Elena Maestrini, Penny Farrar, Maïté Tauber, Suzanne Foley, Richard Holt, Lonnie Zwaigenbaum, David J. Posey, John Tsiantis, Alexander Kolevzon, Agatino Battaglia, Maretha de Jonge, Hilary Coon, Gillian Hughes, John R. Gilbert, Patrick Bolton, Louise Gallagher, Jeff Munson, Kathy White, Michael L. Cuccaro, Annemarie Poustka, Daniel H. Geschwind, Richard Delorme, Annette Estes, Christine M. Freitag, Jillian P. Casey, Joana Almeida, Dalila Pinto, Simon Wallace, Sean Brennan, Stephen J. Guter, Stanley F. Nelson, Michael Rutter, Ghazala Mirza, Anthony J. Bailey, Christina Corsello, Kerstin Wittemeyer, Christian R. Marshall, Janine A. Lamb, Catherine Lord, Hakon Hakonarson, Jiannis Ragoussis, Catalina Betancur, Geraldine Dawson, Eftichia Duketis, Sean Ennis, Fiorella Minopoli, Christopher Gillberg, Vera Stoppioni, Bridget A. Fernandez, Frederico Duque, Eric Fombonne, Ellen M. Wijsman, Bernadette Rogé, Vanessa Hus, Susan E. Folstein, Jonathan L. Haines, Denis C. Shields, Tiago R. Magalhaes, Andrew Green, Thomas Bourgeron, Brian L. Yaspan, Ann P. Thompson, Gudrun Nygren, Judith Miller, Susanne Thomson, Roberta Igliozzi, Ana Filipa Sequeira, Kai Wang, Brett S. Abrahams, John I. Nurnberger, Michael Gill, Thomas H. Wassink, Christopher J. McDougle, Marc N. Coutanche, Anthony P. Monaco, Nadia Bolshakova, Cecilia Kim, Raffaella Tancredi, Rita M. Cantor, Phil Cali, Fred R. Volkmar, Tom Berney, Margaret A. Pericak-Vance, Joachim Hallmayer, Joseph D. Buxbaum, Elena Bacchelli, Latha Soorya, Richard Anney, Regina Regan, University of Bologna, Open University of Israël, IRCCS Fondazione Stella Maris [Pisa], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Goethe-University Frankfurt am Main, Memorial University of Newfoundland [St. John's], McGill University = Université McGill [Montréal, Canada], Johns Hopkins University (JHU), Autism Research Centre and Section of Developmental Psychiatry, University of Cambridge [UK] (CAM), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Psychiatrie génétique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mondor de Recherche Biomédicale, The Hospital for sick children [Toronto] (SickKids), University of Toronto, Australian Resources Research Centre, Kensington, Sécurité et Qualité des Produits d'Origine Végétale (SQPOV), Avignon Université (AU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital des Enfants, CHU Toulouse [Toulouse], School of Chemistry, Dalhousie University [Halifax], DLR Institut für Planetenforschung, Deutsches Zentrum für Luft- und Raumfahrt [Berlin] (DLR), Department of Human Genetics, University of Chicago, University of Alberta, Génétique de l'autisme = Genetics of Autism (NPS-01), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), University of Koblenz-Landau, McMaster University [Hamilton, Ontario], The authors acknowledge the families participating in the study and the main funders of the Autism Genome Project Consortium (AGP): Autism Speaks (USA), the Health Research Board (HRB, Ireland), The Medical Research Council (MRC, UK), Genome Canada/Ontario Genomics Institute, and the Hilibrand Foundation (USA). Additional support for individual groups was provided by the US National Institutes of Health (NIH grants HD055751, HD055782, HD055784, HD35465, MH52708, MH55284, MH57881, MH061009, MH06359, MH066673, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261), the Canadian Institute for Advanced Research (CIFAR), the Canadian Institutes for Health Research (CIHR), Assistance Publique–Hôpitaux de Paris (France), Autistica, Canada Foundation for Innovation/Ontario Innovation Trust, Deutsche Forschungsgemeinschaft (grant Po 255/17-4) (Germany), EC Sixth FP AUTISM MOLGEN, Fundação Calouste Gulbenkian (Portugal), Fondation de France, Fondation FondaMental (France), Fondation Orange (France), Fondation pour la Recherche Médicale (France), Fundação para a Ciência e Tecnologia (Portugal), the Hospital for Sick Children Foundation and University of Toronto (Canada), INSERM (France), Institut Pasteur (France), the Italian Ministry of Health (convention 181 of 19.10.2001), the John P. Hussman Foundation (USA), McLaughlin Centre (Canada), Ontario Ministry of Research and Innovation (Canada), the Seaver Foundation (USA), the Swedish Science Council, The Centre for Applied Genomics (Canada), the Utah Autism Foundation (USA) and the Wellcome Trust core award 075491/Z/04 (UK). We acknowledge support from the Autism Genetic Resource Exchange (AGRE) and Autism Speaks. We gratefully acknowledge the resources provided by the AGRE consortium and the participating AGRE families. AGRE is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to Clara M. Lajonchere (PI). We wish to acknowledge the National Children’s Research Centre Our Lady’s Children’s Hospital Crumlin Ireland for providing additional support and the Wellcome Trust Case–Control Consortium for providing data sets that were used as part of this study. J.P.C is supported by an EMBARK postgraduate award from the Irish Research Council for Science, Engineering and Technology (IRCSET)., The AGRE Consortium, Casey JP, Magalhaes T, Conroy JM, Regan R, Shah N, Anney R, Shields DC, Abrahams BS, Almeida J, Bacchelli E, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bolton PF, Bourgeron T, Brennan S, Cali P, Correia C, Corsello C, Coutanche M, Dawson G, de Jonge M, Delorme R, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Foley S, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Green J, Guter SJ, Hakonarson H, Holt R, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Lamb JA, Leboyer M, Le Couteur A, Leventhal BL, Lord C, Lund SC, Maestrini E, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Miller J, Minopoli F, Mirza GK, Munson J, Nelson SF, Nygren G, Oliveira G, Pagnamenta AT, Papanikolaou K, Parr JR, Parrini B, Pickles A, Pinto D, Piven J, Posey DJ, Poustka A, Poustka F, Ragoussis J, Roge B, Rutter ML, Sequeira AF, Soorya L, Sousa I, Sykes N, Stoppioni V, Tancredi R, Tauber M, Thompson AP, Thomson S, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Vorstman JA, Wallace S, Wang K, Wassink TH, White K, Wing K, Wittemeyer K, Yaspan BL, Zwaigenbaum L, Betancur C, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Geschwind DH, Haines JL, Hallmayer J, Monaco AP, Nurnberger JI Jr, Pericak-Vance MA, Schellenberg GD, Scherer SW, Sutcliffe JS, Szatmari P, Vieland VJ, Wijsman EM, Green A, Gill M, Gallagher L, Vicente A, Ennis S., McGill University, Institut National de la Recherche Agronomique (INRA)-Avignon Université (AU), Neuroscience Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of Bologna/Università di Bologna, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Candidate gene, Genome-wide association study, Linkage Disequilibrium, MESH: Child Development Disorders, Pervasive, Cohort Studies, MESH: Genotype, 0302 clinical medicine, MESH: Child, Cluster Analysis, Genetics(clinical), Copy-number variation, Child, MESH: Cohort Studies, Genetics (clinical), Original Investigation, SNPS, Genetics, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Nuclear Family, MESH: Polymorphism, Single Nucleotide, Homozygote, MESH: Genetic Predisposition to Disease, Middle Aged, Autism spectrum disorder (ASD), 3. Good health, MESH: Linkage Disequilibrium, Female, MESH: DNA Copy Number Variations, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Homozygote, Adult, DNA Copy Number Variations, Genotype, Population, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Nuclear Family, 03 medical and health sciences, HOMOZYGOSITY MAPPING, mental disorders, medicine, Humans, Genetic Predisposition to Disease, ddc:610, AUTISM, GENOME-WIDE ASSOCIATION, education, 030304 developmental biology, MESH: Humans, Genetic heterogeneity, Haplotype, MESH: Adult, MESH: Haplotypes, medicine.disease, MESH: Cluster Analysis, MESH: Male, Haplotypes, Child Development Disorders, Pervasive, Perturbações do Desenvolvimento Infantil e Saúde Mental, MESH: Genome-Wide Association Study, Autism, MESH: Female, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data. Electronic supplementary material The online version of this article (doi:10.1007/s00439-011-1094-6) contains supplementary material, which is available to authorized users.
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23. Genetic variation at the CYP2C19 gene associated with metabolic syndrome susceptibility in a South Portuguese population: results from the pilot study of the European Health Examination Survey in Portugal

Author: Marta Barreto da Silva, Francisco Mendonça, Aida Fernandes, Álvaro Beleza, Mafalda Bourbon, Filomena Horta Correia, Ana Paula Gil, Astrid M. Vicente, Baltazar Nunes, Vânia Gaio, and Carlos Matias Dias
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Context (language use), Single-nucleotide polymorphism, Continuous MetS Score, 030204 cardiovascular system & hematology, Bioinformatics, Doenças Cardio e Cérebro-vasculares, CYP2C19 gene, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Genetic variation, medicine, Internal Medicine, Additive genetic effects, Allele, Genetic Association Study, 030304 developmental biology, Genetic association, Genetic association study, Metabolic Syndrome, 0303 health sciences, business.industry, Research, Confounding, medicine.disease, Metabolic syndrome, 3. Good health, Continuous MetS score, Determinantes da Saúde e da Doença, business
Abstract: BACKGROUND: Metabolic syndrome (MetS) is a cluster of conditions that occur together, increasing the risk of heart disease, stroke and diabetes. Since pathways implicated in different diseases reveal surprising insights into shared genetic bases underlying apparently unrelated traits, we hypothesize that there are common genetic components involved in the clustering of MetS traits. With the aim of identifying these common genetic components, we have performed a genetic association study by integrating MetS traits in a continuous MetS score. METHODS: A cross-sectional study developed in the context of the Portuguese Component of the European Health Examination Survey (EHES) was used. Data was collected through a detailed questionnaire and physical examination. Blood samples were collected and biochemical analyses were performed. Waist circumference, blood pressure, glucose, triglycerides and high density lipoprotein cholesterol (HDL) levels were used to compute a continuous MetS score, obtained by Principal Component Analysis. A total of 37 single nucleotide polymorphisms (SNPs) were genotyped and individually tested for association with the score, adjusting for confounding variables. RESULTS: A total of 206 individuals were studied. Calculated MetS score increased progressively with increasing number of risk factors (P
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24. Compensatory T-cell regulation in unaffected relatives of SLE patients, and opposite IL-2/CD25-mediated effects suggested by coreferentiality modeling.

Author: Constantin Fesel, Marta Barreto, Ricardo C Ferreira, Nuno Costa, Lara L Venda, Clara Pereira, Claudia Carvalho, Maria Francisca Morães-Fontes, Carlos M Ferreira, Carlos Vasconcelos, João F Viana, Eugenia Santos, Berta Martins, Jocelyne Demengeot, and Astrid M Vicente
Subjects: Medicine, Science
Abstract: In human systemic lupus erythematosus (SLE), diverse autoantibodies accumulate over years before disease manifestation. Unaffected relatives of SLE patients frequently share a sustained production of autoantibodies with indiscriminable specificity, usually without ever acquiring the disease. We studied relations of IgG autoantibody profiles and peripheral blood activated regulatory T-cells (aTregs), represented by CD4(+)CD25(bright) T-cells that were regularly 70-90% Foxp3(+). We found consistent positive correlations of broad-range as well as specific SLE-associated IgG with aTreg frequencies within unaffected relatives, but not patients or unrelated controls. Our interpretation: unaffected relatives with shared genetic factors compensated pathogenic effects by aTregs engaged in parallel with the individual autoantibody production. To study this further, we applied a novel analytic approach named coreferentiality that tests the indirect relatedness of parameters in respect to multivariate phenotype data. Results show that independently of their direct correlation, aTreg frequencies and specific SLE-associated IgG were likely functionally related in unaffected relatives: they significantly parallelled each other in their relations to broad-range immunoblot autoantibody profiles. In unaffected relatives, we also found coreferential effects of genetic variation in the loci encoding IL-2 and CD25. A model of CD25 functional genetic effects constructed by coreferentiality maximization suggests that IL-2-CD25 interaction, likely stimulating aTregs in unaffected relatives, had an opposed effect in SLE patients, presumably triggering primarily T-effector cells in this group. Coreferentiality modeling as we do it here could also be useful in other contexts, particularly to explore combined functional genetic effects.
Published: 2012
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24 results on '"Astrid M. Vicente"'

1. How personalised medicine will transform healthcare by 2030: the ICPerMed vision

2. A Role for Gene-Environment Interactions in Autism Spectrum Disorder Is Supported by Variants in Genes Regulating the Effects of Exposure to Xenobiotics

3. Linkage disequilibrium and diversity for three genomic regions in Azoreans and mainland Portuguese

4. Dysfunction of the heteromeric Kv7.3/Kv7.5 potassium channel is associated with autism spectrum disorders

5. Efficacy of focused social and communication intervention practices for young children with autism spectrum disorder: A meta-analysis

6. Definition of a putative pathological region in PARK2 associated with autism spectrum disorder through in silico analysis of its functional structure

7. Identifying disease genes using machine learning and gene functional similarities, assessed through Gene Ontology

8. Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders

9. Association of a Genetic Variant in the ALOX5AP with Higher Risk of Ischemic Stroke: A Case-Control, Meta-Analysis and Functional Study

10. A 3.2 Mb deletion on 18q12 in a patient with childhood autism and high-grade myopia

11. Pharmacogenetics of risperidone response and induced side effects

12. Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levels

13. Brief Report: High Frequency of Biochemical Markers for Mitochondrial Dysfunction in Autism: No Association with the Mitochondrial Aspartate/Glutamate Carrier SLC25A12 Gene

14. Autoantibody repertoires to brain tissue in autism nuclear families

15. Evidence for epistatic gene interactions between growth factor genes in stroke outcome

16. Subject Index Vol. 29, 2010

17. Analysis of the linkage disequilibrium extension in the Azores Islands (Portugal)

18. The Portuguese genetic background in analysis: São Miguel Island (Azores) versus mainland Portugal

19. Study of the genetic relationship and diversity patterns in the Azores based on 15 STR markers

20. Protein interaction networks reveal novel autism risk genes within GWAS statistical noise

21. NCAM and schizophrenia: genetic studies

22. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

23. Genetic variation at the CYP2C19 gene associated with metabolic syndrome susceptibility in a South Portuguese population: results from the pilot study of the European Health Examination Survey in Portugal

24. Compensatory T-cell regulation in unaffected relatives of SLE patients, and opposite IL-2/CD25-mediated effects suggested by coreferentiality modeling.

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24 results on '"Astrid M. Vicente"'

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