25 results on '"Kustanovich V"'
Search Results
2. Biased paternal transmission of SNAP-25 risk alleles in attention-deficit hyperactivity disorder
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Kustanovich, V, Merriman, B, McGough, J, McCracken, J T, Smalley, S L, and Nelson, S F
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- 2003
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3. Efficient discovery of single-nucleotide polymorphisms in coding regions of human genes
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Hu, G, Modreck, B, Riise Stensland, H M F, Saarela, J, Pajukanta, P, Kustanovich, V, Peltonen, L, Nelson, S F, and Lee, C
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- 2002
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4. An efficient method of drying ceramic suspensions
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Aristarkhov, A. I., Bochkareva, L. G., Gamazkova, N. A., Kustanovich, V. G., Rashkovskaya, N. B., Semenova, E. P., and Sinel'nikova, L. L.
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- 1990
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5. Genetic linkage of attention deficit hyperactivity disorder to a region on chromosome 16p13
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Kustanovich, V, Minassian, S, Stone, J, Ogdie, M, McGough, JJ, McCracken, JT, MacPhie, IL, Fisher, SE, Cantor, RM, Monaco, AP, and Nelson, SF
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- 2016
6. Optimization of SBE-TAGS technology for the rapid and cost-effective genotyping of single nucleotide polymorphisms in ADHD
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Stone, J.L., Ogdie, M.N., Kustanovich, V., Crawford, L., Kimura, J., and Nelson, S.
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Attention-deficit hyperactivity disorder -- Genetic aspects ,Genetic disorders -- Research ,Nucleic acid probes ,Biological sciences - Published
- 2001
7. An association study of SNAP-25 alleles shows evidence for biased paternal inheritance in Attention Deficit Hyperactivity Disorder
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Kustanovich, V., Merriman, B., Crawford, L., Smalley, S., and Nelson, S.
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Human genetics -- Research ,Attention-deficit hyperactivity disorder -- Genetic aspects ,Biological sciences - Published
- 2001
8. The characterization and genotyping of Single Nucleotide Polymorphisms in coding regions of brain-expressed Autism candidate genes
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Crawford, L.R., Bailey, J., Merriman, B.L., Kustanovich, V., Smalley, S., and Nelson, S.
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Genetic research -- Analysis ,Human genetics -- Research ,Autism -- Genetic aspects ,Attention-deficit hyperactivity disorder -- Genetic aspects ,Schizophrenia -- Genetic aspects ,Biological sciences - Published
- 2000
9. A Candidate Gene Study of Attention Deficit Hyperactivity Disorder utilizing computationally identified SNPs and a High-Throughput Fluorescent Polarization SNP genotyping assay
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Kustanovich, V., Crawford, L., Kalman, S., Irizarry, K., Brown, N., Lee, C., Smalley, S., and Nelson, S.
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Genetic research -- Analysis ,Human genetics -- Research ,Attention-deficit hyperactivity disorder -- Genetic aspects ,Biological sciences - Published
- 2000
10. A genome-wide scan for common alleles affecting risk for autism
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Anney, R. Klei, L. Pinto, D. Regan, R. Conroy, J. Magalhaes, T.R. Correia, C. Abrahams, B.S. Sykes, N. Pagnamenta, A.T. Almeida, J. Bacchelli, E. Bailey, A.J. Baird, G. Battaglia, A. Berney, T. Bolshakova, N. Bölte, S. Bolton, P.F. Bourgeron, T. Brennan, S. Brian, J. Carson, A.R. Casallo, G. Casey, J. Chu, S.H. Cochrane, L. Corsello, C. Crawford, E.L. Crossett, A. Dawson, G. de Jonge, M. Delorme, R. Drmic, I. Duketis, E. Duque, F. Estes, A. Farrar, P. Fernandez, B.A. Folstein, S.E. Fombonne, E. Freitag, C.M. Gilbert, J. Gillberg, C. Glessner, J.T. Goldberg, J. Green, J. Guter, S.J. Hakonarson, H. Heron, E.A. Hill, M. Holt, R. Howe, J.L. Hughes, G. Hus, V. Igliozzi, R. Kim, C. Klauck, S.M. Kolevzon, A. Korvatska, O. Kustanovich, V. Lajonchere, C.M. Lamb, J.A. Laskawiec, M. Leboyer, M. Le Couteur, A. Leventhal, B.L. Lionel, A.C. Liu, X.-Q. Lord, C. Lotspeich, L. Lund, S.C. Maestrini, E. Mahoney, W. Mantoulan, C. Marshall, C.R. McConachie, H. McDougle, C.J. McGrath, J. McMahon, W.M. Melhem, N.M. Merikangas, A. Migita, O. Minshew, N.J. Mirza, G.K. Munson, J. Nelson, S.F. Noakes, C. Noor, A. Nygren, G. Oliveira, G. Papanikolaou, K. Parr, J.R. Parrini, B. Paton, T. Pickles, A. Piven, J. Posey, D.J. Poustka, A. Poustka, F. Prasad, A. Ragoussis, J. Renshaw, K. Rickaby, J. Roberts, W. Roeder, K. Roge, B. Rutter, M.L. Bierut, L.J. Rice, J.P. Salt, J. Sansom, K. Sato, D. Segurado, R. Senman, L. Shah, N. Sheffield, V.C. Soorya, L. Sousa, I. Stoppioni, V. Strawbridge, C. Tancredi, R. Tansey, K. Thiruvahindrapduram, B. Thompson, A.P. Thomson, S. Tryfon, A. Tsiantis, J. van Engeland, H. Vincent, J.B. Volkmar, F. Wallace, S. Wang, K. Wang, Z. Wassink, T.H. Wing, K. Wittemeyer, K. Wood, S. Yaspan, B.L. Zurawiecki, D. Zwaigenbaum, L. Betancur, C. Buxbaum, J.D. Cantor, R.M. Cook, E.H. Coon, H. Cuccaro, M.L. Gallagher, L. Geschwind, D.H. Gill, M. Haines, J.L. Miller, J. Monaco, A.P. Nurnberger Jr., J.I. Paterson, A.D. Pericak-Vance, M.A. Schellenberg, G.D. Scherer, S.W. Sutcliffe, J.S. Szatmari, P. Vicente, A.M. Vieland, V.J. Wijsman, E.M. Devlin, B. Ennis, S. Hallmayer, J.
- Abstract
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 3 10-28. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10-28 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C. © The Author 2010. Published by Oxford University Press. All rights reserved.
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- 2010
11. Functional impact of global rare copy number variation in autism spectrum disorders
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Pinto, D. Pagnamenta, A.T. Klei, L. Anney, R. Merico, D. Regan, R. Conroy, J. Magalhaes, T.R. Correia, C. Abrahams, B.S. Almeida, J. Bacchelli, E. Bader, G.D. Bailey, A.J. Baird, G. Battaglia, A. Berney, T. Bolshakova, N. Bölte, S. Bolton, P.F. Bourgeron, T. Brennan, S. Brian, J. Bryson, S.E. Carson, A.R. Casallo, G. Casey, J. Chung, B.H.Y. Cochrane, L. Corsello, C. Crawford, E.L. Crossett, A. Cytrynbaum, C. Dawson, G. De Jonge, M. Delorme, R. Drmic, I. Duketis, E. Duque, F. Estes, A. Farrar, P. Fernandez, B.A. Folstein, S.E. Fombonne, E. Freitag, C.M. Gilbert, J. Gillberg, C. Glessner, J.T. Goldberg, J. Green, A. Green, J. Guter, S.J. Hakonarson, H. Heron, E.A. Hill, M. Holt, R. Howe, J.L. Hughes, G. Hus, V. Igliozzi, R. Kim, C. Klauck, S.M. Kolevzon, A. Korvatska, O. Kustanovich, V. Lajonchere, C.M. Lamb, J.A. Laskawiec, M. Leboyer, M. Le Couteur, A. Leventhal, B.L. Lionel, A.C. Liu, X.-Q. Lord, C. Lotspeich, L. Lund, S.C. Maestrini, E. Mahoney, W. Mantoulan, C. Marshall, C.R. McConachie, H. McDougle, C.J. McGrath, J. McMahon, W.M. Merikangas, A. Migita, O. Minshew, N.J. Mirza, G.K. Munson, J. Nelson, S.F. Noakes, C. Noor, A. Nygren, G. Oliveira, G. Papanikolaou, K. Parr, J.R. Parrini, B. Paton, T. Pickles, A. Pilorge, M. Piven, J. Ponting, C.P. Posey, D.J. Poustka, A. Poustka, F. Prasad, A. Ragoussis, J. Renshaw, K. Rickaby, J. Roberts, W. Roeder, K. Roge, B. Rutter, M.L. Bierut, L.J. Rice, J.P. Salt, J. Sansom, K. Sato, D. Segurado, R. Sequeira, A.F. Senman, L. Shah, N. Sheffield, V.C. Soorya, L. Sousa, I. Stein, O. Sykes, N. Stoppioni, V. Strawbridge, C. Tancredi, R. Tansey, K. Thiruvahindrapduram, B. Thompson, A.P. Thomson, S. Tryfon, A. Tsiantis, J. Van Engeland, H. Vincent, J.B. Volkmar, F. Wallace, S. Wang, K. Wang, Z. Wassink, T.H. Webber, C. Weksberg, R. Wing, K. Wittemeyer, K. Wood, S. Wu, J. Yaspan, B.L. Zurawiecki, D. Zwaigenbaum, L. Buxbaum, J.D. Cantor, R.M. Cook, E.H. Coon, H. Cuccaro, M.L. Devlin, B. Ennis, S. Gallagher, L. Geschwind, D.H. Gill, M. Haines, J.L. Hallmayer, J. Miller, J. Monaco, A.P. Nurnberger Jr, J.I. Paterson, A.D. Pericak-Vance, M.A. Schellenberg, G.D. Szatmari, P. Vicente, A.M. Vieland, V.J. Wijsman, E.M. Scherer, S.W. Sutcliffe, J.S. Betancur, C.
- Subjects
mental disorders - Abstract
The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours 1. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability2. Although ASDs are known to be highly heritable ( ∼90%)3, the underlying genetic determinants are still largely unknown.Hereweanalysed the genome-wide characteristics of rare (
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- 2010
12. A genome-wide scan for common alleles affecting risk for autism
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Anney, R., primary, Klei, L., additional, Pinto, D., additional, Regan, R., additional, Conroy, J., additional, Magalhaes, T. R., additional, Correia, C., additional, Abrahams, B. S., additional, Sykes, N., additional, Pagnamenta, A. T., additional, Almeida, J., additional, Bacchelli, E., additional, Bailey, A. J., additional, Baird, G., additional, Battaglia, A., additional, Berney, T., additional, Bolshakova, N., additional, Bolte, S., additional, Bolton, P. F., additional, Bourgeron, T., additional, Brennan, S., additional, Brian, J., additional, Carson, A. R., additional, Casallo, G., additional, Casey, J., additional, Chu, S. H., additional, Cochrane, L., additional, Corsello, C., additional, Crawford, E. L., additional, Crossett, A., additional, Dawson, G., additional, de Jonge, M., additional, Delorme, R., additional, Drmic, I., additional, Duketis, E., additional, Duque, F., additional, Estes, A., additional, Farrar, P., additional, Fernandez, B. A., additional, Folstein, S. E., additional, Fombonne, E., additional, Freitag, C. M., additional, Gilbert, J., additional, Gillberg, C., additional, Glessner, J. T., additional, Goldberg, J., additional, Green, J., additional, Guter, S. J., additional, Hakonarson, H., additional, Heron, E. A., additional, Hill, M., additional, Holt, R., additional, Howe, J. L., additional, Hughes, G., additional, Hus, V., additional, Igliozzi, R., additional, Kim, C., additional, Klauck, S. M., additional, Kolevzon, A., additional, Korvatska, O., additional, Kustanovich, V., additional, Lajonchere, C. M., additional, Lamb, J. A., additional, Laskawiec, M., additional, Leboyer, M., additional, Le Couteur, A., additional, Leventhal, B. L., additional, Lionel, A. C., additional, Liu, X.-Q., additional, Lord, C., additional, Lotspeich, L., additional, Lund, S. C., additional, Maestrini, E., additional, Mahoney, W., additional, Mantoulan, C., additional, Marshall, C. R., additional, McConachie, H., additional, McDougle, C. J., additional, McGrath, J., additional, McMahon, W. M., additional, Melhem, N. M., additional, Merikangas, A., additional, Migita, O., additional, Minshew, N. J., additional, Mirza, G. K., additional, Munson, J., additional, Nelson, S. F., additional, Noakes, C., additional, Noor, A., additional, Nygren, G., additional, Oliveira, G., additional, Papanikolaou, K., additional, Parr, J. R., additional, Parrini, B., additional, Paton, T., additional, Pickles, A., additional, Piven, J., additional, Posey, D. J., additional, Poustka, A., additional, Poustka, F., additional, Prasad, A., additional, Ragoussis, J., additional, Renshaw, K., additional, Rickaby, J., additional, Roberts, W., additional, Roeder, K., additional, Roge, B., additional, Rutter, M. L., additional, Bierut, L. J., additional, Rice, J. P., additional, Salt, J., additional, Sansom, K., additional, Sato, D., additional, Segurado, R., additional, Senman, L., additional, Shah, N., additional, Sheffield, V. C., additional, Soorya, L., additional, Sousa, I., additional, Stoppioni, V., additional, Strawbridge, C., additional, Tancredi, R., additional, Tansey, K., additional, Thiruvahindrapduram, B., additional, Thompson, A. P., additional, Thomson, S., additional, Tryfon, A., additional, Tsiantis, J., additional, Van Engeland, H., additional, Vincent, J. B., additional, Volkmar, F., additional, Wallace, S., additional, Wang, K., additional, Wang, Z., additional, Wassink, T. H., additional, Wing, K., additional, Wittemeyer, K., additional, Wood, S., additional, Yaspan, B. L., additional, Zurawiecki, D., additional, Zwaigenbaum, L., additional, Betancur, C., additional, Buxbaum, J. D., additional, Cantor, R. M., additional, Cook, E. H., additional, Coon, H., additional, Cuccaro, M. L., additional, Gallagher, L., additional, Geschwind, D. H., additional, Gill, M., additional, Haines, J. L., additional, Miller, J., additional, Monaco, A. P., additional, Nurnberger, J. I., additional, Paterson, A. D., additional, Pericak-Vance, M. A., additional, Schellenberg, G. D., additional, Scherer, S. W., additional, Sutcliffe, J. S., additional, Szatmari, P., additional, Vicente, A. M., additional, Vieland, V. J., additional, Wijsman, E. M., additional, Devlin, B., additional, Ennis, S., additional, and Hallmayer, J., additional
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- 2010
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13. Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD: confirmation of association of ADHD with DRD4 and DRD5
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Kustanovich, V, primary, Ishii, J, additional, Crawford, L, additional, Yang, M, additional, McGough, J J, additional, McCracken, J T, additional, Smalley, S L, additional, and Nelson, S F, additional
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- 2003
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14. Selection of optimum heat treatment for punches of [Cr−W−Si] steel 6KhV2S
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Kustanovich, V. S.
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- 1960
- Full Text
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15. Individual common variants exert weak effects on the risk for autism spectrum disorderspi
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Naisha Shah, William M. McMahon, Barbara Parrini, Jeremy R. Parr, Thomas Bourgeron, Vanessa Hus, Gudrun Nygren, Sabine M. Klauck, John B. Vincent, Nadine M. Melhem, Jillian P. Casey, Christina Corsello, Jonathan L. Haines, Andrew D. Paterson, Raffaella Tancredi, Alistair T. Pagnamenta, Jonathan Green, Richard Delorme, Geraldine Dawson, Andrew Pickles, Carine Mantoulan, Alexander Kolevzon, Bridget A. Fernandez, Frederico Duque, Inês Sousa, Tara Paton, Kathryn Roeder, Joana Almeida, Richard Anney, Margaret A. Pericak-Vance, Joachim Hallmayer, Gerard D. Schellenberg, Sabata C. Lund, Rita M. Cantor, Daniel H. Geschwind, Janine A. Lamb, Annette Estes, Sven Bölte, Hakon Hakonarson, Gillian Hughes, Gillian Baird, John I. Nurnberger, Jessica Brian, Bernie Devlin, Roberta Igliozzi, Vera Stoppioni, Jiannis Ragoussis, Peter Szatmari, Ghazala Mirza, Eric Fombonne, Thomas H. Wassink, Emily L. Crawford, Nuala Sykes, Danielle Zurawiecki, Graham Kenny, David J. Posey, Elena Maestrini, Vlad Kustanovich, Elena Bacchelli, Veronica J. Vieland, Stephen W. Scherer, Guiomar Oliveira, Simon Wallace, John R. Gilbert, Latha Soorya, Sean Brennan, Tiago R. Magalhaes, Hilary Coon, Elizabeth A. Heron, Sabine Schlitt, Fritz Poustka, Astrid M. Vicente, Patrick Bolton, Linda Lotspeich, Nancy J. Minshew, Val C. Sheffield, Bennett L. Leventhal, Xiao-Qing Liu, Andrew Green, Joseph D. Buxbaum, Shawn Wood, Susan E. Folstein, Sean Ennis, Catarina Correia, James S. Sutcliffe, Carolyn Noakes, Ann Le Couteur, Marion Leboyer, Ann P. Thompson, Christine M. Freitag, Fred R. Volkmar, Katerina Papanikolaou, Dalila Pinto, Agatino Battaglia, Frances Lombard, Joseph Piven, Maretha de Jonge, Michael Rutter, Clara Lajonchere, Kerstin Wittemeyer, Herman van Engeland, Michael L. Cuccaro, Richard Holt, Lonnie Zwaigenbaum, Louise Gallagher, Jeff Munson, Ana Tryfon, John Tsiantis, Lambertus Klei, Christopher Gillberg, Penny Farrar, Joseph T. Glessner, Ellen M. Wijsman, Anthony P. Monaco, Wendy Roberts, Nadia Bolshakova, Cecilia Kim, Judith Miller, Stephen J. Guter, Susanne Thomson, Catherine Lord, Anthony J. Bailey, Miriam Law-Smith, Michael Gill, Christopher J. McDougle, Bernadette Rogé, Alison K. Merikangas, Jacob A. S. Vorstman, Suma Jacob, Judith Conroy, Kirsty Wing, Regina Regan, Jennifer L. Howe, Stanley F. Nelson, Edwin H. Cook, Catalina Betancur, Eftichia Duketis, Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The Centre for Applied Genomics, Toronto, University of Toronto-The Hospital for sick children [Toronto] (SickKids)-Department of Molecular Genetics-McLaughlin Centre, Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Newcomen Centre, Guy's Hospital [London], Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Department of Child and Adolescent Psychiatry, Institute of psychiatry, Molecular and Cellular Neurobiology, Autism Research Unit, The Hospital for sick children [Toronto] (SickKids)-University of Toronto, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Autism and Communicative Disorders Centre, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Department of Psychiatry, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Service de psychopathologie de l'enfant et de l'adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Speech and Hearing Sciences [Washington], University of Washington [Seattle], The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Disciplines of Genetics and Medicine, Memorial University of Newfoundland [St. John's], University of Miami School of Medicine, John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], Research Unit on Children's Psychosocial Maladjustment, Université Laval [Québec] (ULaval)-Department of Psychology, University of Gothenburg (GU), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Manchester Academic Health Sciences Centre, Department of Disability and Human Development, University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Department of Psychiatry and Behavioral Sciences [Stanford], Stanford Medicine, Stanford University-Stanford University, Human Genetics Center, The University of Texas Health Science Center at Houston (UTHealth), Autism Genetic Resource Exchange, Autism Speaks, Centre for Integrated Genomic Medical Research, Manchester, University of Manchester [Manchester], Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, European Network of Bipolar Research Expert Centres (ENBREC), ENBREC, Newcastle University [Newcastle]-Institute of Health & Society (Child & Adolescent Psychiatry), New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Centre de Référence du Syndrome de Prader-Willi, CHU Toulouse [Toulouse], Indiana University School of Medicine, Indiana University System-Indiana University System, Department of Psychiatry and Behavioral Sciences, University Department of Child Psychiatry, National and Kapodistrian University of Athens (NKUA), Department of Medicine, Manchester, University of Manchester [Manchester]-School of Epidemiology and Health Science, Department of Statistics, Carnegie Mellon University [Pittsburgh] (CMU), Octogone Unité de Recherche Interdisciplinaire (Octogone), Université Toulouse - Jean Jaurès (UT2J), Social, Genetic and Developmental Psychiatry Centre, Department of Pediatrics, University of Iowa [Iowa City]-Howard Hughes Medical-Institute Carver College of Medicine, Neuropsichiatria Infantile, Ospedale Santa Croce, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, University of Toronto, Child Study Centre, Yale University School of Medicine, University of Oxford [Oxford]-Warneford Hospital, University of Alberta, MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), The Institute of Psychiatry-King‘s College London, Department of Human Genetics, Los Angeles, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California-University of California [Los Angeles] (UCLA), University of California-University of California, Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris [Pisa], Autism Speaks and the Department of Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Neurology, University of California-University of California-David Geffen School of Medicine [Los Angeles], Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institutes of Neuroscience and Health and Society, Newcastle University [Newcastle], Carolina Institute for Developmental Disabilities, Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Departments of Biostatistics and Medicine, Physiopathologie des Maladies du Système Nerveux Central, 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), Stanford School of Medicine [Stanford], Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, Children’s Hospital of Philadelphia (CHOP )-Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], The Hospital for sick children [Toronto] (SickKids)-University of Toronto-Department of Molecular Genetics-McLaughlin Centre, Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Yale School of Medicine [New Haven, Connecticut] (YSM), King‘s College London-The Institute of Psychiatry, University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Anney R, Klei L, Pinto D, Almeida J, Bacchelli E, Baird G, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Casey J, Conroy J, Correia C, Corsello C, Crawford EL, de Jonge M, Delorme R, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Gilbert J, Gillberg C, Glessner JT, Green A, Green J, Guter SJ, Heron EA, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Jacob S, Kenny GP, Kim C, Kolevzon A, Kustanovich V, Lajonchere CM, Lamb JA, Law-Smith M, Leboyer M, Le Couteur A, Leventhal BL, Liu XQ, Lombard F, Lord C, Lotspeich L, Lund SC, Magalhaes TR, Mantoulan C, McDougle CJ, Melhem NM, Merikangas A, Minshew NJ, Mirza GK, Munson J, Noakes C, Nygren G, Papanikolaou K, Pagnamenta AT, Parrini B, Paton T, Pickles A, Posey DJ, Poustka F, Ragoussis J, Regan R, Roberts W, Roeder K, Roge B, Rutter ML, Schlitt S, Shah N, Sheffield VC, Soorya L, Sousa I, Stoppioni V, Sykes N, Tancredi R, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Vorstman J, Wallace S, Wing K, Wittemeyer K, Wood S, Zurawiecki D, Zwaigenbaum L, Bailey AJ, Battaglia A, Cantor RM, Coon H, Cuccaro ML, Dawson G, Ennis S, Freitag CM, Geschwind DH, Haines JL, Klauck SM, McMahon WM, Maestrini E, Miller J, Monaco AP, Nelson SF, Nurnberger JI Jr, Oliveira G, Parr JR, Pericak-Vance MA, Piven J, Schellenberg GD, Scherer SW, Vicente AM, Wassink TH, Wijsman EM, Betancur C, Buxbaum JD, Cook EH, Gallagher L, Gill M, Hallmayer J, Paterson AD, Sutcliffe JS, Szatmari P, Vieland VJ, Hakonarson H, Devlin B, University of Oxford, Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University of Oxford-Warneford Hospital, University of Pennsylvania, University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP ), Betancur, Catalina, and Université de Toulouse (UT)-Université de Toulouse (UT)
- Subjects
Male ,CNTNAP2 ,Genotype ,Genome-wide association study ,Single-nucleotide polymorphism ,Nerve Tissue Proteins ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Biology ,Language Development ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,autism spectrum disorders (ASDs) ,Gene Frequency ,Risk Factors ,mental disorders ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Copy-number variation ,Allele ,GENOME-WIDE ASSOCIATION ,Child ,Molecular Biology ,Allele frequency ,Genetics (clinical) ,Alleles ,030304 developmental biology ,0303 health sciences ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Association Studies Articles ,Membrane Proteins ,General Medicine ,medicine.disease ,Genetic architecture ,Child Development Disorders, Pervasive ,common variant ,Perturbações do Desenvolvimento Infantil e Saúde Mental ,Autism ,Female ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
International audience; While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
- Published
- 2012
16. A genome-wide scan for common alleles affecting risk for autism
- Author
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Veronica J. Vieland, Stephen W. Scherer, Elizabeth A. Heron, Barbara Parrini, Jeremy R. Parr, Louise Gallagher, Jeff Munson, Annemarie Poustka, Susan E. Folstein, Irene Drmic, Gudrun Nygren, John P. Rice, Jeff Salt, Simon Wallace, Geraldine Dawson, Daniel H. Geschwind, Annette Estes, Sean Brennan, Alistair T. Pagnamenta, Nancy J. Minshew, Christina Corsello, Jonathan Green, William M. McMahon, Christopher Gillberg, Kathryn Roeder, Lambertus Klei, Anath C. Lionel, Bridget A. Fernandez, Thomas Bourgeron, Ellen M. Wijsman, Gerard D. Schellenberg, Wendy Roberts, Jeremy Goldberg, Frederico Duque, Ghazala Mirza, Sean Ennis, Joana Almeida, Nadine M. Melhem, Jillian P. Casey, Roberta Igliozzi, Ricardo Segurado, Carine Mantoulan, Katy Renshaw, Kai Wang, Andrew D. Paterson, Raffaella Tancredi, Matthew Nicholas Hill, Richard Anney, Christian R. Marshall, Anthony P. Monaco, Linda Lotspeich, Marion Leboyer, Richard Holt, Andrew Pickles, Vlad Kustanovich, William M. Mahoney, Jessica Brian, Inês Sousa, Peter Szatmari, Vanessa Hus, Janine A. Lamb, Hakon Hakonarson, Lonnie Zwaigenbaum, John Tsiantis, David J. Posey, Olena Korvatska, Guillermo Casallo, Rita M. Cantor, Bhooma Thiruvahindrapduram, Nadia Bolshakova, Sven Bölte, Alison K. Merikangas, Brian L. Yaspan, Cecilia Kim, Andrew Crossett, Fritz Poustka, Danielle Zurawiecki, Agatino Battaglia, Sabata C. Lund, Ann P. Thompson, Bennett L. Leventhal, Jessica Rickaby, Zhouzhi Wang, John I. Nurnberger, Astrid M. Vicente, Maretha de Jonge, Tiago R. Magalhaes, Michael L. Cuccaro, Val C. Sheffield, Nuala Sykes, Elena Maestrini, Guiomar Oliveira, Joseph D. Buxbaum, Fred R. Volkmar, Shawn Wood, Magdalena Laskawiec, Katherine Sansom, Herman van Engeland, Jane McGrath, Thomas H. Wassink, Su H. Chu, Elena Bacchelli, Carolyn Noakes, Ann Le Couteur, Catarina Correia, Ohsuke Migita, Bernie Devlin, Hilary Coon, Gillian Baird, Joseph Piven, Tom Berney, Ana Tryfon, Abdul Noor, Patrick Bolton, Latha Soorya, Vera Stoppioni, Stephen J. Guter, Joseph T. Glessner, Michael Gill, Christopher J. McDougle, Anthony J. Bailey, Margaret A. Pericak-Vance, Joachim Hallmayer, Christine M. Freitag, Penny Farrar, Kirsty Wing, Katherine E. Tansey, Bernadette Rogé, Michael Rutter, Christina Strawbridge, Brett S. Abrahams, Kerstin Wittemeyer, Laura J. Bierut, Tara Paton, Emily L. Crawford, Jonathan L. Haines, Alexander Kolevzon, Gillian Hughes, Lili Senman, James S. Sutcliffe, John B. Gilbert, Katerina Papanikolaou, Andrew R. Carson, Lynne E Cochrane, Regina Regan, Judith Miller, Susanne Thomson, Helen McConachie, Daisuke Sato, Richard Delorme, Jiannis Ragoussis, Eric Fombonne, Clara Lajonchere, Judith Conroy, Dalila Pinto, Aparna Prasad, Naisha Shah, Stanley F. Nelson, Sabine M. Klauck, Catalina Betancur, John B. Vincent, Eftichia Duketis, Jennifer L. Howe, Edwin H. Cook, Xiao-Qing Liu, Catherine Lord, Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), 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, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Department of Psychiatry, University of Oxford [Oxford]-Warneford Hospital, Newcomen Centre, Guy's Hospital [London], Department of Psychiatry and Behavioral Sciences [Stanford], Stanford Medicine, Stanford University-Stanford University, Child and Adolescent Mental Health, Newcastle University [Newcastle], Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Department of Child and Adolescent Psychiatry, Institute of psychiatry, Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Autism Research Unit, University of Toronto-The Hospital for sick children [Toronto] (SickKids), Autism and Communicative Disorders Centre, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Department of Statistics, Carnegie Mellon University [Pittsburgh] (CMU), Scientific Affairs, Autism Speaks, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Service de psychopathologie de l'enfant et de l'adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Department of Speech and Hearing Sciences [Washington], University of Washington [Seattle], Disciplines of Genetics and Medicine, Memorial University of Newfoundland [St. John's], John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], Department of Child Psychiatry, McGill University = Université McGill [Montréal, Canada]-Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC)-McGill University Health Center [Montreal] (MUHC), University of Gothenburg (GU), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario], Manchester Academic Health Sciences Centre, Institute for Juvenile Research-University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Human Genetics Center, The University of Texas Health Science Center at Houston (UTHealth), Department of Medicine, Autism Genetic Resource Exchange, Centre for Integrated Genomic Medical Research, Manchester, University of Manchester [Manchester], Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Nathan Kline Institute for Psychiatric Research (NKI), Nathan Kline Institute for Psychiatric Research, New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU)-NYU Child Study Center, Centre d'Etudes et de Recherches en PsychoPathologie, Université Toulouse - Jean Jaurès (UT2J), Indiana University School of Medicine, Indiana University System-Indiana University System, Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris [Pisa], Departments of Psychiatry and Neurology, Department of Psychiatry and Behavioral Sciences, Department of Human Genetics, Los Angeles, David Geffen School of Medicine [Los Angeles], University of California-University of California-University of California [Los Angeles] (UCLA), Centre for Addiction and Mental Health, Clarke Institute, University Department of Child Psychiatry, National and Kapodistrian University of Athens (NKUA), Institutes of Neuroscience and Health and Society, Department of Medicine, Manchester, University of Manchester [Manchester]-School of Epidemiology and Health Science, Carolina Institute for Developmental Disabilities, Social, Genetic and Developmental Psychiatry Centre, Washington University in Saint Louis (WUSTL), Howard Hughes Medical-Institute Carver College of Medicine-University of Iowa [Iowa City], Neuropsichiatria Infantile, Ospedale Santa Croce, Child Study Centre, Yale University School of Medicine, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], University of Alberta, Physiopathologie des Maladies du Système Nerveux Central, 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), Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, Departments of Biostatistics and Medicine, This research was primarily supported by 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 [HD055751, HD055782, HD055784, HD35465, MH52708, MH55284, MH057881, MH061009, MH06359, MH066673, MH077930, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261], 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), GlaxoSmithKline-CIHR Pathfinder Chair (Canada), 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), Netherlands Organization for Scientific Research [Rubicon 825.06.031], Ontario Ministry of Research and Innovation (Canada), Royal Netherlands Academy of Arts and Sciences [TMF/DA/5801], 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]. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422)., University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], University of California (UC)-University of California (UC), The Hospital for sick children [Toronto] (SickKids)-University of Toronto, Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), University of Iowa [Iowa City]-Howard Hughes Medical-Institute Carver College of Medicine, Yale School of Medicine [New Haven, Connecticut] (YSM), 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), University of Oxford, University of Oxford-Warneford Hospital, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP ), Université de Toulouse (UT)-Université de Toulouse (UT), University of Pennsylvania, Betancur, Catalina, Anney R, Klei L, Pinto D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Sykes N, Pagnamenta AT, Almeida J, Bacchelli E, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Carson AR, Casallo G, Casey J, Chu SH, Cochrane L, Corsello C, Crawford EL, Crossett A, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Melhem NM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Piven J, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Wing K, Wittemeyer K, Wood S, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Betancur C, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Gallagher L, Geschwind DH, Gill M, Haines JL, Miller J, Monaco AP, Nurnberger JI Jr, Paterson AD, Pericak-Vance MA, Schellenberg GD, Scherer SW, Sutcliffe JS, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Devlin B, Ennis S, and Hallmayer J.
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Genome-wide association study ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,MESH: Genotype ,0302 clinical medicine ,Risk Factors ,MESH: Risk Factors ,Databases, Genetic ,Copy-number variation ,MESH: Genetic Variation ,Genetics (clinical) ,MESH: Databases, Genetic ,Genetics ,0303 health sciences ,education.field_of_study ,MESH: Polymorphism, Single Nucleotide ,Association Studies Articles ,MESH: Genetic Predisposition to Disease ,General Medicine ,MESH: European Continental Ancestry Group ,Autism spectrum disorders ,MESH: DNA Copy Number Variations ,Genotyping ,DNA Copy Number Variations ,Genotype ,Population ,MESH: Autistic Disorder ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,White People ,03 medical and health sciences ,Genetic variation ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Allele ,Autistic Disorder ,SNP association ,education ,Molecular Biology ,Alleles ,MESH: Genome, Human ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Humans ,Genome, Human ,MESH: Alleles ,Haplotype ,Genetic Variation ,Genetic architecture ,Perturbações do Desenvolvimento Infantil e Saúde Mental ,MESH: Genome-Wide Association Study ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C. Author has checked copyright TS 14.06.13 The subscript characters from the abstract have not copied across properly. TS
- Published
- 2010
17. Considerations regarding maintenance therapy for acute myeloid leukemia in remission.
- Author
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Schiller GJ and Kustanovich V
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- Adult, Humans, Remission Induction, Recurrence, Leukemia, Myeloid, Acute drug therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Introduction: For most adult patients with acute myeloid leukemia, relapse is characteristic of the disease. When allotransplant in first complete remission is administered as consolidative therapy, relapse is still common, affecting 20-40% of recipients. Maintenance of remission with low-dose treatments may hold promise in preventing relapse., Areas Covered: Improvements in the detection of clinical and biological variants of disease allow the practitioner to identify which patients, based on disease features, may benefit from therapy directed at residual clonal elements that might contribute to relapse. Along with improvements in methods of detecting residual disease, novel agents are under investigation as a platform in order to maintain remission and may contribute to prolonged survival. In this manuscript, we review literature available through PubMed regarding the use of maintenance therapy, described as post-remission or post-transplant treatment intended to delay or prevent relapse., Expert Opinion: Although results of randomized studies are limited, a role for maintenance therapy, particularly directed at molecular targets, in distinct settings of post-remission management is recommended. We also advise that randomized studies of immune therapy along with opportunities for further evaluation of risk-agnostic interventions be a focus of cooperative groups.
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- 2024
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- View/download PDF
18. Individual common variants exert weak effects on the risk for autism spectrum disorders.
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Anney R, Klei L, Pinto D, Almeida J, Bacchelli E, Baird G, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Casey J, Conroy J, Correia C, Corsello C, Crawford EL, de Jonge M, Delorme R, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Gilbert J, Gillberg C, Glessner JT, Green A, Green J, Guter SJ, Heron EA, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Jacob S, Kenny GP, Kim C, Kolevzon A, Kustanovich V, Lajonchere CM, Lamb JA, Law-Smith M, Leboyer M, Le Couteur A, Leventhal BL, Liu XQ, Lombard F, Lord C, Lotspeich L, Lund SC, Magalhaes TR, Mantoulan C, McDougle CJ, Melhem NM, Merikangas A, Minshew NJ, Mirza GK, Munson J, Noakes C, Nygren G, Papanikolaou K, Pagnamenta AT, Parrini B, Paton T, Pickles A, Posey DJ, Poustka F, Ragoussis J, Regan R, Roberts W, Roeder K, Roge B, Rutter ML, Schlitt S, Shah N, Sheffield VC, Soorya L, Sousa I, Stoppioni V, Sykes N, Tancredi R, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Vorstman JA, Wallace S, Wing K, Wittemeyer K, Wood S, Zurawiecki D, Zwaigenbaum L, Bailey AJ, Battaglia A, Cantor RM, Coon H, Cuccaro ML, Dawson G, Ennis S, Freitag CM, Geschwind DH, Haines JL, Klauck SM, McMahon WM, Maestrini E, Miller J, Monaco AP, Nelson SF, Nurnberger JI Jr, Oliveira G, Parr JR, Pericak-Vance MA, Piven J, Schellenberg GD, Scherer SW, Vicente AM, Wassink TH, Wijsman EM, Betancur C, Buxbaum JD, Cook EH, Gallagher L, Gill M, Hallmayer J, Paterson AD, Sutcliffe JS, Szatmari P, Vieland VJ, Hakonarson H, and Devlin B
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- Alleles, Child, Child Development Disorders, Pervasive physiopathology, Female, Gene Frequency, Genotype, Humans, Language Development, Male, Polymorphism, Single Nucleotide, Risk Factors, Child Development Disorders, Pervasive genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Membrane Proteins genetics, Nerve Tissue Proteins genetics
- Abstract
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
- Published
- 2012
- Full Text
- View/download PDF
19. Nutrition, weight gain and eating behavior in pregnancy: a review of experimental evidence for long-term effects on the risk of obesity in offspring.
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Sen S, Carpenter AH, Hochstadt J, Huddleston JY, Kustanovich V, Reynolds AA, and Roberts S
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- Animals, Female, Humans, Male, Obesity epidemiology, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Risk Factors, Feeding Behavior psychology, Nutritional Status, Obesity etiology, Weight Gain physiology
- Abstract
Obesity has reached near epidemic proportions in the developed world. As reproductive age women are a part of this trend, the effect of maternal obesity on the developing fetus must be investigated. In this review, we evaluated the experimental evidence relating maternal nutritional status and eating behavior before and during pregnancy on the risk of obesity in the offspring. The studies were compiled and selected based on their methodologies, study design and relevance. The analyzed studies were compiled to quantify, if possible, the relationship between maternal and offspring weight. Descriptive and observational studies were also included if they were seminal in the field. Based on the current data, maternal obesity is a critical factor exacerbating multigenerational obesity. Mechanistic studies, mainly in animals, have identified potential areas for intervention which might limit transmission of adverse risk factors for obesity from mothers to infants during pregnancy., (Copyright © 2012 Elsevier Inc. All rights reserved.)
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- 2012
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20. Functional impact of global rare copy number variation in autism spectrum disorders.
- Author
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Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader GD, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Bryson SE, Carson AR, Casallo G, Casey J, Chung BH, Cochrane L, Corsello C, Crawford EL, Crossett A, Cytrynbaum C, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green A, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Pilorge M, Piven J, Ponting CP, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Sequeira AF, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stein O, Sykes N, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Webber C, Weksberg R, Wing K, Wittemeyer K, Wood S, Wu J, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Devlin B, Ennis S, Gallagher L, Geschwind DH, Gill M, Haines JL, Hallmayer J, Miller J, Monaco AP, Nurnberger JI Jr, Paterson AD, Pericak-Vance MA, Schellenberg GD, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Scherer SW, Sutcliffe JS, and Betancur C
- Subjects
- Case-Control Studies, Cell Movement, Child, Child Development Disorders, Pervasive pathology, Cytoprotection, Europe ethnology, Genome-Wide Association Study, Humans, Signal Transduction, Social Behavior, Child Development Disorders, Pervasive genetics, Child Development Disorders, Pervasive physiopathology, DNA Copy Number Variations genetics, Gene Dosage genetics, Genetic Predisposition to Disease genetics
- Abstract
The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
- Published
- 2010
- Full Text
- View/download PDF
21. Microduplications of 16p11.2 are associated with schizophrenia.
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McCarthy SE, Makarov V, Kirov G, Addington AM, McClellan J, Yoon S, Perkins DO, Dickel DE, Kusenda M, Krastoshevsky O, Krause V, Kumar RA, Grozeva D, Malhotra D, Walsh T, Zackai EH, Kaplan P, Ganesh J, Krantz ID, Spinner NB, Roccanova P, Bhandari A, Pavon K, Lakshmi B, Leotta A, Kendall J, Lee YH, Vacic V, Gary S, Iakoucheva LM, Crow TJ, Christian SL, Lieberman JA, Stroup TS, Lehtimäki T, Puura K, Haldeman-Englert C, Pearl J, Goodell M, Willour VL, Derosse P, Steele J, Kassem L, Wolff J, Chitkara N, McMahon FJ, Malhotra AK, Potash JB, Schulze TG, Nöthen MM, Cichon S, Rietschel M, Leibenluft E, Kustanovich V, Lajonchere CM, Sutcliffe JS, Skuse D, Gill M, Gallagher L, Mendell NR, Craddock N, Owen MJ, O'Donovan MC, Shaikh TH, Susser E, Delisi LE, Sullivan PF, Deutsch CK, Rapoport J, Levy DL, King MC, and Sebat J
- Subjects
- Humans, Risk Factors, Chromosomes, Human, Pair 16, Gene Duplication, Genetic Predisposition to Disease, Schizophrenia genetics
- Abstract
Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 x 10(-5), OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 x 10(-7)), bipolar disorder (P = 0.017) and autism (P = 1.9 x 10(-7)). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 x 10(-13)). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).
- Published
- 2009
- Full Text
- View/download PDF
22. Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes.
- Author
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Bucan M, Abrahams BS, Wang K, Glessner JT, Herman EI, Sonnenblick LI, Alvarez Retuerto AI, Imielinski M, Hadley D, Bradfield JP, Kim C, Gidaya NB, Lindquist I, Hutman T, Sigman M, Kustanovich V, Lajonchere CM, Singleton A, Kim J, Wassink TH, McMahon WM, Owley T, Sweeney JA, Coon H, Nurnberger JI, Li M, Cantor RM, Minshew NJ, Sutcliffe JS, Cook EH, Dawson G, Buxbaum JD, Grant SF, Schellenberg GD, Geschwind DH, and Hakonarson H
- Subjects
- Adolescent, Calcium-Binding Proteins, Case-Control Studies, Cell Adhesion Molecules, Neuronal, Child, Child, Preschool, Cohort Studies, Female, Gene Duplication, Humans, Male, Nerve Tissue Proteins genetics, Neural Cell Adhesion Molecules, Pedigree, Sequence Deletion, Ubiquitin-Protein Ligases genetics, Young Adult, Autistic Disorder genetics, Exons, Gene Dosage, Genetic Predisposition to Disease, Genome-Wide Association Study
- Abstract
The genetics underlying the autism spectrum disorders (ASDs) is complex and remains poorly understood. Previous work has demonstrated an important role for structural variation in a subset of cases, but has lacked the resolution necessary to move beyond detection of large regions of potential interest to identification of individual genes. To pinpoint genes likely to contribute to ASD etiology, we performed high density genotyping in 912 multiplex families from the Autism Genetics Resource Exchange (AGRE) collection and contrasted results to those obtained for 1,488 healthy controls. Through prioritization of exonic deletions (eDels), exonic duplications (eDups), and whole gene duplication events (gDups), we identified more than 150 loci harboring rare variants in multiple unrelated probands, but no controls. Importantly, 27 of these were confirmed on examination of an independent replication cohort comprised of 859 cases and an additional 1,051 controls. Rare variants at known loci, including exonic deletions at NRXN1 and whole gene duplications encompassing UBE3A and several other genes in the 15q11-q13 region, were observed in the course of these analyses. Strong support was likewise observed for previously unreported genes such as BZRAP1, an adaptor molecule known to regulate synaptic transmission, with eDels or eDups observed in twelve unrelated cases but no controls (p = 2.3x10(-5)). Less is known about MDGA2, likewise observed to be case-specific (p = 1.3x10(-4)). But, it is notable that the encoded protein shows an unexpectedly high similarity to Contactin 4 (BLAST E-value = 3x10(-39)), which has also been linked to disease. That hundreds of distinct rare variants were each seen only once further highlights complexity in the ASDs and points to the continued need for larger cohorts., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2009
- Full Text
- View/download PDF
23. A unified genetic theory for sporadic and inherited autism.
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Zhao X, Leotta A, Kustanovich V, Lajonchere C, Geschwind DH, Law K, Law P, Qiu S, Lord C, Sebat J, Ye K, and Wigler M
- Subjects
- Autistic Disorder classification, Autistic Disorder epidemiology, Databases, Factual, Female, Humans, Male, Models, Genetic, Risk Factors, Sex Characteristics, Societies, Medical, Autistic Disorder genetics, Autistic Disorder pathology, Genetic Predisposition to Disease genetics
- Abstract
Autism is among the most clearly genetically determined of all cognitive-developmental disorders, with males affected more often than females. We have analyzed autism risk in multiplex families from the Autism Genetic Resource Exchange (AGRE) and find strong evidence for dominant transmission to male offspring. By incorporating generally accepted rates of autism and sibling recurrence, we find good fit for a simple genetic model in which most families fall into two types: a small minority for whom the risk of autism in male offspring is near 50%, and the vast majority for whom male offspring have a low risk. We propose an explanation that links these two types of families: sporadic autism in the low-risk families is mainly caused by spontaneous mutation with high penetrance in males and relatively poor penetrance in females; and high-risk families are from those offspring, most often females, who carry a new causative mutation but are unaffected and in turn transmit the mutation in dominant fashion to their offspring.
- Published
- 2007
- Full Text
- View/download PDF
24. Genetic linkage of attention-deficit/hyperactivity disorder on chromosome 16p13, in a region implicated in autism.
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Smalley SL, Kustanovich V, Minassian SL, Stone JL, Ogdie MN, McGough JJ, McCracken JT, MacPhie IL, Francks C, Fisher SE, Cantor RM, Monaco AP, and Nelson SF
- Subjects
- Chromosome Mapping, Female, Humans, Male, Attention Deficit Disorder with Hyperactivity genetics, Autistic Disorder genetics, Chromosomes, Human, Pair 16, Genetic Linkage genetics
- Abstract
Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed behavioral disorder in childhood and likely represents an extreme of normal behavior. ADHD significantly impacts learning in school-age children and leads to impaired functioning throughout the life span. There is strong evidence for a genetic etiology of the disorder, although putative alleles, principally in dopamine-related pathways suggested by candidate-gene studies, have very small effect sizes. We use affected-sib-pair analysis in 203 families to localize the first major susceptibility locus for ADHD to a 12-cM region on chromosome 16p13 (maximum LOD score 4.2; P=.000005), building upon an earlier genomewide scan of this disorder. The region overlaps that highlighted in three genome scans for autism, a disorder in which inattention and hyperactivity are common, and physically maps to a 7-Mb region on 16p13. These findings suggest that variations in a gene on 16p13 may contribute to common deficits found in both ADHD and autism.
- Published
- 2002
- Full Text
- View/download PDF
25. Genome-wide analysis of single-nucleotide polymorphisms in human expressed sequences.
- Author
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Irizarry K, Kustanovich V, Li C, Brown N, Nelson S, Wong W, and Lee CJ
- Subjects
- Base Sequence, Chromosome Mapping, Colony-Stimulating Factors genetics, GPI-Linked Proteins, Gene Library, Genetic Diseases, Inborn genetics, Genetic Markers, Humans, Membrane Glycoproteins, Mesothelin, Models, Genetic, Models, Statistical, Molecular Sequence Data, Polymorphism, Restriction Fragment Length, Sequence Alignment, Sequence Homology, Nucleic Acid, Chromosomes, Human, Pair 22, Expressed Sequence Tags, Genome, Human, HLA-A Antigens genetics, Polymorphism, Genetic, Proteins genetics
- Abstract
Single-nucleotide polymorphisms (SNPs) have been explored as a high-resolution marker set for accelerating the mapping of disease genes. Here we report 48,196 candidate SNPs detected by statistical analysis of human expressed sequence tags (ESTs), associated primarily with coding regions of genes. We used Bayesian inference to weigh evidence for true polymorphism versus sequencing error, misalignment or ambiguity, misclustering or chimaeric EST sequences, assessing data such as raw chromatogram height, sharpness, overlap and spacing, sequencing error rates, context-sensitivity and cDNA library origin. Three separate validations-comparison with 54 genes screened for SNPs independently, verification of HLA-A polymorphisms and restriction fragment length polymorphism (RFLP) testing-verified 70%, 89% and 71% of our predicted SNPs, respectively. Our method detects tenfold more true HLA-A SNPs than previous analyses of the EST data. We found SNPs in a large fraction of known disease genes, including some disease-causing mutations (for example, the HbS sickle-cell mutation). Our comprehensive analysis of human coding region polymorphism provides a public resource for mapping of disease genes (available at http://www.bioinformatics.ucla.edu/snp).
- Published
- 2000
- Full Text
- View/download PDF
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