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326 results on '"Vieland, Veronica J."'

1. Absolutely Zero Evidence

Author

Vieland, Veronica J.

Subjects
Statistics - Other Statistics
Abstract

Statistical analysis is often used to evaluate the evidence for or against scientific hypotheses, and various statistics (e.g., p-values, likelihood ratios, Bayes factors) are interpreted as measures of evidence strength. Here I consider evidence measurement from the point of view of representational measurement theory, and argue that familiar evidence statistics do not conform to any legitimate measurement scale type. I then consider the notion of an absolute scale for evidence measurement, in a sense to be defined, focusing particularly on the notion of absolute 0 evidence, which turns out to be something other than what one might have expected.

Published
2018

3. Host-to-host variation of ecological interactions in polymicrobial infections

Author

Mukherjee, Sayak, Weimer, Kristin E., Seok, Sang-Cheol, Ray, Will C., Jayaprakash, C., Vieland, Veronica J., Swords, W. Edward, and Das, Jayajit

Subjects
Quantitative Biology - Populations and Evolution, Condensed Matter - Statistical Mechanics
Abstract

Host-to-host variability with respect to interactions between microorganisms and multicellular hosts are commonly observed in infection and in homeostasis. However, the majority of mechanistic models used in analyzing host-microorganism relationships, as well as most of the ecological theories proposed to explain co-evolution of host and microbes, are based on averages across a host population. By assuming that observed variations are random and independent, these models overlook the role of inter-host differences. Here we analyze mechanisms underlying host-to-host variations, using the well-characterized experimental infection model of polymicrobial otitis media (OM) in chinchillas, in combination with population dynamic models and a Maximum Entropy (MaxEnt) based inference scheme. We find that the nature of the interactions among bacterial species critically regulates host-to-host variations of these interactions. Surprisingly, seemingly unrelated phenomena, such as the efficiency of individual bacterial species in utilizing nutrients for growth and the microbe-specific host immune response, can become interdependent in a host population. The latter finding suggests a potential mechanism that could lead to selection of specific strains of bacterial species during the coevolution of the host immune response and the bacterial species., Comment: 39 Pages 6 figures

Published
2014
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5. In silico Modeling of Itk Activation Kinetics in Thymocytes Suggests Competing Positive and Negative IP4 Mediated Feedbacks Increase Robustness

Author

Mukherjee, Sayak, Rigaud, Stephanie, Seok, Sang-Cheol, Fu, Guo, Prochenka, Agnieszka, Dworkin, Michael, Gascoigne, Nicholas R. J., Vieland, Veronica J., Sauer, Karsten, and Das, Jayajit

Subjects
Quantitative Biology - Cell Behavior, Quantitative Biology - Quantitative Methods
Abstract

The inositol-phosphate messenger inositol(1,3,4,5)tetrakisphosphate (IP4) is essential for thymocyte positive selection by regulating plasma-membrane association of the protein tyrosine kinase Itk downstream of the T cell receptor (TCR). IP4 can act as a soluble analog of the phosphoinositide 3-kinase (PI3K) membrane lipid product phosphatidylinositol(3,4,5)trisphosphate (PIP3). PIP3 recruits signaling proteins such as Itk to cellular membranes by binding to PH and other domains. In thymocytes, low-dose IP4 binding to the Itk PH domain surprisingly promoted and high-dose IP4 inhibited PIP3 binding of Itk PH domains. However, the mechanisms that underlie the regulation of membrane recruitment of Itk by IP4 and PIP3 remain unclear. The distinct Itk PH domain ability to oligomerize is consistent with a cooperative-allosteric mode of IP4 action. However, other possibilities cannot be ruled out due to difficulties in quantitatively measuring the interactions between Itk, IP4 and PIP3, and in generating non-oligomerizing Itk PH domain mutants. This has hindered a full mechanistic understanding of how IP4 controls Itk function. By combining experimentally measured kinetics of PLC{\gamma}1 phosphorylation by Itk with in silico modeling of multiple Itk signaling circuits and a maximum entropy (MaxEnt) based computational approach, we show that those in silico models which are most robust against variations of protein and lipid expression levels and kinetic rates at the single cell level share a cooperative-allosteric mode of Itk regulation by IP4 involving oligomeric Itk PH domains at the plasma membrane. This identifies MaxEnt as an excellent tool for quantifying robustness for complex TCR signaling circuits and provides testable predictions to further elucidate a controversial mechanism of PIP3 signaling.

Published
2013
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6. Cell responses only partially shape cell-to-cell variations in protein abundances in Escherichia coli chemotaxis

Author

Mukherjee, Sayak, Seok, Sang-Cheol, Vieland, Veronica J., and Das, Jayajit

Subjects
Quantitative Biology - Cell Behavior, Condensed Matter - Statistical Mechanics, Quantitative Biology - Molecular Networks
Abstract

Cell-to-cell variations in protein abundance in clonal cell populations are ubiquitous in living systems. Since protein composition determines responses in individual cells, it stands to reason that the variations themselves are subject to selective pressures. But the functional role of these cell-to-cell differences is not well understood. One way to tackle questions regarding relationships between form and function is to perturb the form (e.g., change the protein abundances) and observe the resulting changes in some function. Here we take on the form-function relationship from the inverse perspective, asking instead what specific constraints on cell-to-cell variations in protein abundance are imposed by a given functional phenotype. We develop a maximum entropy (MaxEnt) based approach to posing questions of this type, and illustrate the method by application to the well characterized chemotactic response in Escherichia coli (E. coli). We find that full determination of observed cell-to-cell variations in protein abundances is not inherent in chemotaxis itself, but in fact appears to be jointly imposed by the chemotaxis program in conjunction with other factors, e.g., the protein synthesis machinery and/or additional non-chemotactic cell functions such as cell metabolism. These results illustrate the power of MaxEnt as a tool for the investigation of relationships between biological form and function., Comment: 51 Pages, 18 Figures

Published
2013
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7. Data-driven quantification of robustness and sensitivity of cell signaling networks

Author

Mukherjee, Sayak, Seok, Sang-Cheol, Vieland, Veronica J., and Das, Jayajit

Subjects
Quantitative Biology - Quantitative Methods, Quantitative Biology - Molecular Networks
Abstract

Robustness and sensitivity of responses generated by cell signaling networks has been associated with survival and evolvability of organisms. However, existing methods analyzing robustness and sensitivity of signaling networks ignore the experimentally observed cell-to-cell variations of protein abundances and cell functions or contain ad hoc assumptions. We propose and apply a data driven Maximum Entropy (MaxEnt) based method to quantify robustness and sensitivity of Escherichia coli (E. coli) chemotaxis signaling network. Our analysis correctly rank orders different models of E. coli chemotaxis based on their robustness and suggests that parameters regulating cell signaling are evolutionary selected to vary in individual cells according to their abilities to perturb cell functions. Furthermore, predictions from our approach regarding distribution of protein abundances and properties of chemotactic responses in individual cells based on cell population averaged data are in excellent agreement with their experimental counterparts. Our approach is general and can be used to evaluate robustness as well as generate predictions of single cell properties based on population averaged experimental data in a wide range of cell signaling systems., Comment: 46 pages, 11 figures. Physical Biology, 2013

Published
2013
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8. Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders

Author

Pinto, Dalila, Delaby, Elsa, Merico, Daniele, Barbosa, Mafalda, Merikangas, Alison, Klei, Lambertus, Thiruvahindrapuram, Bhooma, Xu, Xiao, Ziman, Robert, Wang, Zhuozhi, Vorstman, Jacob AS, Thompson, Ann, Regan, Regina, Pilorge, Marion, Pellecchia, Giovanna, Pagnamenta, Alistair T, Oliveira, Bárbara, Marshall, Christian R, Magalhaes, Tiago R, Lowe, Jennifer K, Howe, Jennifer L, Griswold, Anthony J, Gilbert, John, Duketis, Eftichia, Dombroski, Beth A, De Jonge, Maretha V, Cuccaro, Michael, Crawford, Emily L, Correia, Catarina T, Conroy, Judith, Conceição, Inês C, Chiocchetti, Andreas G, Casey, Jillian P, Cai, Guiqing, Cabrol, Christelle, Bolshakova, Nadia, Bacchelli, Elena, Anney, Richard, Gallinger, Steven, Cotterchio, Michelle, Casey, Graham, Zwaigenbaum, Lonnie, Wittemeyer, Kerstin, Wing, Kirsty, Wallace, Simon, van Engeland, Herman, Tryfon, Ana, Thomson, Susanne, Soorya, Latha, Rogé, Bernadette, Roberts, Wendy, Poustka, Fritz, Mouga, Susana, Minshew, Nancy, McInnes, L Alison, McGrew, Susan G, Lord, Catherine, Leboyer, Marion, Le Couteur, Ann S, Kolevzon, Alexander, González, Patricia Jiménez, Jacob, Suma, Holt, Richard, Guter, Stephen, Green, Jonathan, Green, Andrew, Gillberg, Christopher, Fernandez, Bridget A, Duque, Frederico, Delorme, Richard, Dawson, Geraldine, Chaste, Pauline, Café, Cátia, Brennan, Sean, Bourgeron, Thomas, Bolton, Patrick F, Bölte, Sven, Bernier, Raphael, Baird, Gillian, Bailey, Anthony J, Anagnostou, Evdokia, Almeida, Joana, Wijsman, Ellen M, Vieland, Veronica J, Vicente, Astrid M, Schellenberg, Gerard D, Pericak-Vance, Margaret, Paterson, Andrew D, Parr, Jeremy R, Oliveira, Guiomar, Nurnberger, John I, Monaco, Anthony P, Maestrini, Elena, Klauck, Sabine M, Hakonarson, Hakon, Haines, Jonathan L, Geschwind, Daniel H, Freitag, Christine M, Folstein, Susan E, and Ennis, Sean

Subjects
Genetics, Brain Disorders, Pediatric, Mental Health, Intellectual and Developmental Disabilities (IDD), Neurosciences, Autism, 2.1 Biological and endogenous factors, Aetiology, Child, Child Development Disorders, Pervasive, DNA Copy Number Variations, Female, Gene Regulatory Networks, Humans, Male, Metabolic Networks and Pathways, Multigene Family, Pedigree, Sequence Deletion, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

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

9. Absolutely Zero Evidence.

Author

Vieland, Veronica J. and Seok, Sang-Cheol

Subjects
*HYPOTHESIS, *SCALING (Social sciences), *STATISTICS
Abstract

Statistical analysis is often used to evaluate the strength of evidence for or against scientific hypotheses. Here we consider evidence measurement from the point of view of representational measurement theory, focusing in particular on the 0-points of measurement scales. We argue that a properly calibrated evidence measure will need to count up from absolute 0, in a sense to be defined, and that this 0-point is likely to be something other than what one might have expected. This suggests the need for a new theory of statistical evidence in the context of which calibrated evidence measurement becomes tractable. [ABSTRACT FROM AUTHOR]

Published
2023
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11. A genome-wide association analysis of loss of ambulation in dystrophinopathy patients suggests multiple candidate modifiers of disease severity

Author

Flanigan, Kevin M., primary, Waldrop, Megan A., additional, Martin, Paul T., additional, Alles, Roxane, additional, Dunn, Diane M., additional, Alfano, Lindsay N., additional, Simmons, Tabatha R., additional, Moore-Clingenpeel, Melissa, additional, Burian, John, additional, Seok, Sang-Cheol, additional, Weiss, Robert B., additional, and Vieland, Veronica J., additional

Published
2023
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12. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

Author

Szatmari, Peter, Paterson, Andrew D, Zwaigenbaum, Lonnie, Roberts, Wendy, Brian, Jessica, Liu, Xiao-Qing, Vincent, John B, Skaug, Jennifer L, Thompson, Ann P, Senman, Lili, Feuk, Lars, Qian, Cheng, Bryson, Susan E, Jones, Marshall B, Marshall, Christian R, Scherer, Stephen W, Vieland, Veronica J, Bartlett, Christopher, Mangin, La Vonne, Goedken, Rhinda, Segre, Alberto, Pericak-Vance, Margaret A, Cuccaro, Michael L, Gilbert, John R, Wright, Harry H, Abramson, Ruth K, Betancur, Catalina, Bourgeron, Thomas, Gillberg, Christopher, Leboyer, Marion, Buxbaum, Joseph D, Davis, Kenneth L, Hollander, Eric, Silverman, Jeremy M, Hallmayer, Joachim, Lotspeich, Linda, Sutcliffe, James S, Haines, Jonathan L, Folstein, Susan E, Piven, Joseph, Wassink, Thomas H, Sheffield, Val, Geschwind, Daniel H, Bucan, Maja, Brown, W Ted, Cantor, Rita M, Constantino, John N, Gilliam, T Conrad, Herbert, Martha, LaJonchere, Clara, Ledbetter, David H, Lese-Martin, Christa, Miller, Janet, Nelson, Stan, Samango-Sprouse, Carol A, Spence, Sarah, State, Matthew, Tanzi, Rudolph E, Coon, Hilary, Dawson, Geraldine, Devlin, Bernie, Estes, Annette, Flodman, Pamela, Klei, Lambertus, McMahon, William M, Minshew, Nancy, Munson, Jeff, Korvatska, Elena, Rodier, Patricia M, Schellenberg, Gerard D, Smith, Moyra, Spence, M Anne, Stodgell, Chris, Tepper, Ping Guo, Wijsman, Ellen M, Yu, Chang-En, Roge, Bernadette, Mantoulan, Carine, Wittemeyer, Kerstin, Poustka, Annemarie, Felder, Barbel, Klauck, Sabine M, Schuster, Claudia, Poustka, Fritz, Boelte, Sven, Feineis-Matthews, Sabine, Herbrecht, Evelyn, Schmoetzer, Gabi, Tsiantis, John, Papanikolaou, Katerina, Maestrini, Elena, Bacchelli, Elena, Blasi, Francesca, Carone, Simona, Toma, Claudio, Van Engeland, Herman, de Jonge, Maretha, Kemner, Chantal, Koop, Frederike, and Langemeijer, Marjolijn

Subjects
Biological Sciences, Genetics, Human Genome, Brain Disorders, Intellectual and Developmental Disabilities (IDD), Mental Health, Pediatric Research Initiative, Pediatric, Autism, Autistic Disorder, Chromosome Aberrations, Chromosome Mapping, Family, Female, Genetic Linkage, Genetic Predisposition to Disease, Genetic Testing, Genetic Variation, Humans, Lod Score, Male, Risk Factors, Autism Genome Project Consortium, glutamic acid, neurexin, neuroligin, adult, analytical equipment, article, autism, chromosome 11p, chromosome rearrangement, controlled study, family, female, gene locus, gene mapping, genetic analysis, genetic linkage, genetic risk, genetic variability, human, major clinical study, male, microarray analysis, priority journal, sample size, single nucleotide polymorphism, synaptogenesis, Genetic Screening, Linkage, Variation, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

Published
2007

13. Mapping autism risk loci using genetic linkage and chromosomal rearrangements.

Author

Autism Genome Project Consortium, Szatmari, Peter, Paterson, Andrew D, Zwaigenbaum, Lonnie, Roberts, Wendy, Brian, Jessica, Liu, Xiao-Qing, Vincent, John B, Skaug, Jennifer L, Thompson, Ann P, Senman, Lili, Feuk, Lars, Qian, Cheng, Bryson, Susan E, Jones, Marshall B, Marshall, Christian R, Scherer, Stephen W, Vieland, Veronica J, Bartlett, Christopher, Mangin, La Vonne, Goedken, Rhinda, Segre, Alberto, Pericak-Vance, Margaret A, Cuccaro, Michael L, Gilbert, John R, Wright, Harry H, Abramson, Ruth K, Betancur, Catalina, Bourgeron, Thomas, Gillberg, Christopher, Leboyer, Marion, Buxbaum, Joseph D, Davis, Kenneth L, Hollander, Eric, Silverman, Jeremy M, Hallmayer, Joachim, Lotspeich, Linda, Sutcliffe, James S, Haines, Jonathan L, Folstein, Susan E, Piven, Joseph, Wassink, Thomas H, Sheffield, Val, Geschwind, Daniel H, Bucan, Maja, Brown, W Ted, Cantor, Rita M, Constantino, John N, Gilliam, T Conrad, Herbert, Martha, Lajonchere, Clara, Ledbetter, David H, Lese-Martin, Christa, Miller, Janet, Nelson, Stan, Samango-Sprouse, Carol A, Spence, Sarah, State, Matthew, Tanzi, Rudolph E, Coon, Hilary, Dawson, Geraldine, Devlin, Bernie, Estes, Annette, Flodman, Pamela, Klei, Lambertus, McMahon, William M, Minshew, Nancy, Munson, Jeff, Korvatska, Elena, Rodier, Patricia M, Schellenberg, Gerard D, Smith, Moyra, Spence, M Anne, Stodgell, Chris, Tepper, Ping Guo, Wijsman, Ellen M, Yu, Chang-En, Rogé, Bernadette, Mantoulan, Carine, Wittemeyer, Kerstin, Poustka, Annemarie, Felder, Bärbel, Klauck, Sabine M, Schuster, Claudia, Poustka, Fritz, Bölte, Sven, Feineis-Matthews, Sabine, Herbrecht, Evelyn, Schmötzer, Gabi, Tsiantis, John, Papanikolaou, Katerina, Maestrini, Elena, Bacchelli, Elena, Blasi, Francesca, Carone, Simona, Toma, Claudio, Van Engeland, Herman, de Jonge, Maretha, Kemner, Chantal, and Koop, Frederieke

Subjects
Autism Genome Project Consortium, Humans, Chromosome Aberrations, Genetic Predisposition to Disease, Risk Factors, Chromosome Mapping, Family, Autistic Disorder, Lod Score, Female, Male, Genetic Variation, Genetic Testing, Genetic Linkage, Intellectual and Developmental Disabilities (IDD), Pediatric Research Initiative, Human Genome, Pediatric, Brain Disorders, Genetics, Autism, Mental Health, glutamic acid, neurexin, neuroligin, adult, analytical equipment, article, autism, chromosome 11p, chromosome rearrangement, controlled study, family, female, gene locus, gene mapping, genetic analysis, genetic linkage, genetic risk, genetic variability, human, major clinical study, male, microarray analysis, priority journal, sample size, single nucleotide polymorphism, synaptogenesis, Genetic Screening, Linkage, Variation, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

Published
2007

14. Performance comparison of two-point linkage methods using microsatellite markers flanking known disease locations

Author

Logue, Mark W, George, Andrew W, Spence, M Anne, and Vieland, Veronica J

Subjects
genetically complex traits, affected relative pairs, posterior probability, lod scores, locus, power, strategies, models
Abstract

The Genetic Analysis Workshop 14 simulated data presents an interesting, challenging, and plausible example of a complex disease interaction in a dataset. This paper summarizes the ease of detection for each of the simulated Kofendrerd Personality Disorder (KPD) genes across all of the replicates for five standard linkage statistics. Using the KPD affection status, we have analyzed the microsatellite markers flanking each of the disease genes, plus an additional 2 markers that were not linked to any of the disease loci. All markers were analyzed using the following two-point linkage methods: 1) a MMLS, which is a standard admixture LOD score maximized over θ, α, and mode of inheritance, 2) a MLS calculated by GENEHUNTER, 3) the Kong and Cox LOD score as computed by MERLIN, 4) a MOD score (standard heterogeneity LOD maximized over θ, α, and a grid of genetic model parameters), and 5) the PPL, a Bayesian statistic that directly measures the strength of evidence for linkage to a marker. All of the major loci (D1–D4) were detectable with varying probabilities in the different populations. However, the modifier genes (D5 and D6) were difficult to detect, with similar distributions under the null and alternative across populations and statistics. The pooling of the four datasets in each replicate (n = 350 pedigrees) greatly improved the chance of detecting the major genes using all five methods, but failed to increase the chance to detect D5 and D6.

Published
2005

15. Evaluation of the chromosome 2q37.3 gene CENTG2 as an autism susceptibility gene

Author

Wassink, Thomas H, Piven, Joseph, Vieland, Veronica J, Jenkins, Laura, Frantz, Rebecca, Bartlett, Christopher W, Goedken, Rhinda, Childress, Deb, Spence, M Anne, Smith, Moyra, and Sheffield, Val C

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Research, Intellectual and Developmental Disabilities (IDD), Pediatric, Neurosciences, Brain Disorders, Autism, Mental Health, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Mental health, ADP-Ribosylation Factors, Amino Acid Sequence, Autistic Disorder, Chromosome Deletion, Chromosomes, Human, Pair 2, DNA Mutational Analysis, Family Health, Female, GTPase-Activating Proteins, Genetic Linkage, Genetic Predisposition to Disease, Genotype, Humans, Lod Score, Male, Microsatellite Repeats, Mutation, Polymorphism, Genetic, Sequence Homology, Amino Acid, Telomere, linkage, linkage disequilibrium, autistic disorder, chromosomal abnormalities, Autistic disorder, Chromosomal abnormalities, Linkage, Linkage disequilibrium, arginine, glycine, serine, amino acid substitution, article, autism, CENTG2 gene, chromosome 2q, developmental disorder, DNA polymorphism, fluorescence in situ hybridization, gene, gene deletion, gene linkage disequilibrium, genetic analysis, genetic linkage, genetic susceptibility, genotype, human, priority journal, Clinical Sciences, Clinical sciences
Abstract

Autism is a highly heritable neurodevelopmental syndrome with a complex genetic etiology for which no disease genes have yet been definitively identified. We ascertained three subjects with autism spectrum disorders and chromosome 2q37.3 terminal deletions, and refined the deletion breakpoint regions using polymorphism mapping and fluorescence in situ hybridization (FISH) probes. We then genotyped polymorphic markers downstream from the breakpoint region in a sample of autism affected sibling pair families. Both the chromosomal breakpoints and linkage analyses focused our attention on the gene centaurin gamma-2 (CENTG2), an attractive candidate gene based also on its function and pattern of expression. We therefore assessed CENTG2 for its involvement in autism by (1) screening its exons for variants in 199 autistic and 160 non-autistic individuals, and (2) genotyping and assessing intra-genic polymorphisms for linkage and linkage disequilibrium (LD). The exon screen revealed a Ser --> Gly substitution in one proband, an Arg --> Gly substitution in another, and a number of additional variants unique to the autism families. No unique variants were found in the control subjects. The genotyping produced strong evidence for linkage from two intronic polymorphisms, with a maximum two-point HLOD value of 3.96 and a posterior probability of linkage (PPL) of 51%. These results were contradicted, however, by substantially weaker evidence for linkage from multi-point analyses and by no evidence of LD. We conclude, therefore, that 2q37.3 continues to be a region of interest for autism susceptibility, and that CENTG2 is an intriguing candidate gene that merits further scrutiny for its role in autism.

Published
2005

18. Using extended pedigrees to identify novel autism spectrum disorder (ASD) candidate genes

Author

Woodbury-Smith, Marc, Paterson, Andrew D., Thiruvahindrapduram, Bhooma, Lionel, Anath C., Marshall, Christian R., Merico, Daniele, Fernandez, Bridget A., Duku, Eric, Sutcliffe, James S., O’Conner, Irene, Chrysler, Christina, Thompson, Ann, Kellam, Barbara, Tammimies, Kristiina, Walker, Susan, Yuen, Ryan K. C., Uddin, Mohammed, Howe, Jennifer L., Parlier, Morgan, Whitten, Kathy, Szatmari, Peter, Vieland, Veronica J., Piven, Joseph, and Scherer, Stephen W.

Published
2015
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23. Candidate gene modifiers of dystrophinopathy identified by the uniform application of genome-wide datasets to novel GWAS-identified loci

Author

Flanigan, Kevin M, primary, Waldrop, Megan A., additional, Martin, Paul T., additional, Alles, Roxane, additional, Dunn, Diane M., additional, Alfano, Lindsay N., additional, Simmons, Tabatha R., additional, Moore-Clingenpeel, Melissa, additional, Burian, John, additional, Seok, Sang-Cheol, additional, Vieland, Veronica J., additional, and Weiss, Robert B., additional

Published
2021
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24. A genome-wide association analysis of loss of ambulation in dystrophinopathy patients suggests multiple candidate modifiers of disease severity

Author

Flanigan, Kevin M., primary, Waldrop, Megan A., additional, Martin, Paul T., additional, Alles, Roxane, additional, Dunn, Diane M., additional, Alfano, Lindsay N., additional, Simmons, Tabatha R., additional, Moore-Clingenpeel, Melissa, additional, Burian, John, additional, Seok, Sang-Cheol, additional, Weiss, Robert B., additional, and Vieland, Veronica J., additional

Published
2021
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37. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Author

Casey, Jillian P., Magalhaes, Tiago, Conroy, Judith M., Regan, Regina, Shah, Naisha, Anney, Richard, Shields, Denis C., Abrahams, Brett S., Almeida, Joana, Bacchelli, Elena, Bailey, Anthony J., Baird, Gillian, Battaglia, Agatino, Berney, Tom, Bolshakova, Nadia, Bolton, Patrick F., Bourgeron, Thomas, Brennan, Sean, Cali, Phil, Correia, Catarina, Corsello, Christina, Coutanche, Marc, Dawson, Geraldine, de Jonge, Maretha, Delorme, Richard, Duketis, Eftichia, Duque, Frederico, Estes, Annette, Farrar, Penny, Fernandez, Bridget A., Folstein, Susan E., Foley, Suzanne, Fombonne, Eric, Freitag, Christine M., Gilbert, John, Gillberg, Christopher, Glessner, Joseph T., Green, Jonathan, Guter, Stephen J., Hakonarson, Hakon, Holt, Richard, Hughes, Gillian, Hus, Vanessa, Igliozzi, Roberta, Kim, Cecilia, Klauck, Sabine M., Kolevzon, Alexander, Lamb, Janine A., Leboyer, Marion, Le Couteur, Ann, Leventhal, Bennett L., Lord, Catherine, Lund, Sabata C., Maestrini, Elena, Mantoulan, Carine, Marshall, Christian R., McConachie, Helen, McDougle, Christopher J., McGrath, Jane, McMahon, William M., Merikangas, Alison, Miller, Judith, Minopoli, Fiorella, Mirza, Ghazala K., Munson, Jeff, Nelson, Stanley F., Nygren, Gudrun, Oliveira, Guiomar, Pagnamenta, Alistair T., Papanikolaou, Katerina, Parr, Jeremy R., Parrini, Barbara, Pickles, Andrew, Pinto, Dalila, Piven, Joseph, Posey, David J., Poustka, Annemarie, Poustka, Fritz, Ragoussis, Jiannis, Roge, Bernadette, Rutter, Michael L., Sequeira, Ana F., Soorya, Latha, Sousa, Inês, Sykes, Nuala, Stoppioni, Vera, Tancredi, Raffaella, Tauber, Maïté, Thompson, Ann P., Thomson, Susanne, Tsiantis, John, Van Engeland, Herman, Vincent, John B., Volkmar, Fred, Vorstman, Jacob A. S., Wallace, Simon, Wang, Kai, Wassink, Thomas H., White, Kathy, Wing, Kirsty, Wittemeyer, Kerstin, Yaspan, Brian L., Zwaigenbaum, Lonnie, Betancur, Catalina, Buxbaum, Joseph D., Cantor, Rita M., Cook, Edwin H., Coon, Hilary, Cuccaro, Michael L., Geschwind, Daniel H., Haines, Jonathan L., Hallmayer, Joachim, Monaco, Anthony P., Nurnberger, Jr., John I., Pericak-Vance, Margaret A., Schellenberg, Gerard D., Scherer, Stephen W., Sutcliffe, James S., Szatmari, Peter, Vieland, Veronica J., Wijsman, Ellen M., Green, Andrew, Gill, Michael, Gallagher, Louise, Vicente, Astrid, and Ennis, Sean

Published
2012
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39. A multilocus model of the genetic architecture of autoimmune thyroid disorder, with clinical implications

Author

Vieland, Veronica J., Yungui Huang, Bartlett, Christopher, Davies, Terry F., and Tomer, Yaron

Subjects
Thyroiditis, Autoimmune -- Research, Thyroiditis, Autoimmune -- Genetic aspects, Biological models -- Usage, Phenotype -- Research, Biological sciences
Abstract

The development of a preliminary model of the genetic architecture of autoimmune thyroid disorder (AITD) is reported. The data obtained from use of model for the incorporation of information from multiple sources, combined with careful modeling of distinct intermediate phenotypes can provide insights into the genetic architecture of complex diseases.

Published
2008

43. SRGAP1 Is a Candidate Gene for Papillary Thyroid Carcinoma Susceptibility

Author

He, Huiling, Bronisz, Agnieszka, Liyanarachchi, Sandya, Nagy, Rebecca, Li, Wei, Huang, Yungui, Akagi, Keiko, Saji, Motoyasu, Kula, Dorota, Wojcicka, Anna, Sebastian, Nikhil, Wen, Bernard, Puch, Zbigniew, Kalemba, Michal, Stachlewska, Elzbieta, Czetwertynska, Malgorzata, Dlugosinska, Joanna, Dymecka, Kinga, Ploski, Rafal, Krawczyk, Marek, Morrison, Patrick J., Ringel, Matthew D., Kloos, Richard T., Jazdzewski, Krystian, Symer, David E., Vieland, Veronica J., Ostrowski, Michael, Jarząb, Barbara, and de la Chapelle, Albert

Published
2013

44. MLIP: using multiple processors to compute the posterior probability of linkage

Author

Vieland Veronica J, Segre Alberto M, and Govil Manika

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Localization of complex traits by genetic linkage analysis may involve exploration of a vast multidimensional parameter space. The posterior probability of linkage (PPL), a class of statistics for complex trait genetic mapping in humans, is designed to model the trait model complexity represented by the multidimensional parameter space in a mathematically rigorous fashion. However, the method requires the evaluation of integrals with no functional form, making it difficult to compute, and thus further test, develop and apply. This paper describes MLIP, a multiprocessor two-point genetic linkage analysis system that supports statistical calculations, such as the PPL, based on the full parameter space implicit in the linkage likelihood. Results The fundamental question we address here is whether the use of additional processors effectively reduces total computation time for a PPL calculation. We use a variety of data – both simulated and real – to explore the question "how close can we get?" to linear speedup. Empirical results of our study show that MLIP does significantly speed up two-point log-likelihood ratio calculations over a grid space of model parameters. Conclusion Observed performance of the program is dependent on characteristics of the data including granularity of the parameter grid space being explored and pedigree size and structure. While work continues to further optimize performance, the current version of the program can already be used to efficiently compute the PPL. Thanks to MLIP, full multidimensional genome scans are now routinely being completed at our centers with runtimes on the order of days, not months or years.

Published
2008
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46. The emperor's new methods

Author

Spence, M. Anne, Greenberg, David A., Hodge, Susan E., and Vieland, Veronica J.

Subjects
Genetic research -- Methods, Methodology -- Analysis, Biological sciences
Published
2003

47. Individual common variants exert weak effects on the risk for autism spectrum disorderspi

Author

Anney, Richard, Klei, Lambertus, Pinto, Dalila, Almeida, Joana, Bacchelli, Elena, Baird, Gillian, Bolshakova, Nadia, Bölte, Sven, Bolton, Patrick F., Bourgeron, Thomas, Brennan, Sean, Brian, Jessica, Casey, Jillian, Conroy, Judith, Correia, Catarina, Corsello, Christina, Crawford, Emily L., de Jonge, Maretha, Delorme, Richard, Duketis, Eftichia, Duque, Frederico, Estes, Annette, Farrar, Penny, Fernandez, Bridget A., Folstein, Susan E., Fombonne, Eric, Gilbert, John, Gillberg, Christopher, Glessner, Joseph T., Green, Andrew, Green, Jonathan, Guter, Stephen J., Heron, Elizabeth A., Holt, Richard, Howe, Jennifer L., Hughes, Gillian, Hus, Vanessa, Igliozzi, Roberta, Jacob, Suma, Kenny, Graham P., Kim, Cecilia, Kolevzon, Alexander, Kustanovich, Vlad, Lajonchere, Clara M., Lamb, Janine A., Law-Smith, Miriam, Leboyer, Marion, Le Couteur, Ann, Leventhal, Bennett L., Liu, Xiao-Qing, Lombard, Frances, Lord, Catherine, Lotspeich, Linda, Lund, Sabata C., Magalhaes, Tiago R., Mantoulan, Carine, McDougle, Christopher J., Melhem, Nadine M., Merikangas, Alison, Minshew, Nancy J., Mirza, Ghazala K., Munson, Jeff, Noakes, Carolyn, Nygren, Gudrun, Papanikolaou, Katerina, Pagnamenta, Alistair T., Parrini, Barbara, Paton, Tara, Pickles, Andrew, Posey, David J., Poustka, Fritz, Ragoussis, Jiannis, Regan, Regina, Roberts, Wendy, Roeder, Kathryn, Roge, Bernadette, Rutter, Michael L., Schlitt, Sabine, Shah, Naisha, Sheffield, Val C., Soorya, Latha, Sousa, Inês, Stoppioni, Vera, Sykes, Nuala, Tancredi, Raffaella, Thompson, Ann P., Thomson, Susanne, Tryfon, Ana, Tsiantis, John, Van Engeland, Herman, Vincent, John B., Volkmar, Fred, Vorstman, JAS, Wallace, Simon, Wing, Kirsty, Wittemeyer, Kerstin, Wood, Shawn, Zurawiecki, Danielle, Zwaigenbaum, Lonnie, Bailey, Anthony J., Battaglia, Agatino, Cantor, Rita M., Coon, Hilary, Cuccaro, Michael L., Dawson, Geraldine, Ennis, Sean, Freitag, Christine M., Geschwind, Daniel H., Haines, Jonathan L., Klauck, Sabine M., McMahon, William M., Maestrini, Elena, Miller, Judith, Monaco, Anthony P., Nelson, Stanley F., Nurnberger, John I., Jr., Oliveira, Guiomar, Parr, Jeremy R., Pericak-Vance, Margaret A., Piven, Joseph, Schellenberg, Gerard D., Scherer, Stephen W., Vicente, Astrid M., Wassink, Thomas H., Wijsman, Ellen M., Betancur, Catalina, Buxbaum, Joseph D., Cook, Edwin H., Gallagher, Louise, Gill, Michael, Hallmayer, Joachim, Paterson, Andrew D., Sutcliffe, James S., Szatmari, Peter, Vieland, Veronica J., Hakonarson, Hakon, and Devlin, Bernie

Published
2012
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48. A major susceptibility locus for specific language impairment is located on 13q21

Author

Bartlett, Christopher W., Flax, Judy F., Logue, Mark W., Vieland, Veronica J., Bassett, Anne S., Tallal, Paula, and Brzustowicz, Linda M.

Subjects
Language disorders in children -- Genetic aspects, Linkage (Genetics) -- Analysis, Chromosome mapping -- Analysis, Genetic disorders -- Analysis, Biological sciences
Published
2002

50. Rare familial 16q21 microdeletions under a linkage peak implicate cadherin 8 (CDH8) in susceptibility to autism and learning disability

Author

Pagnamenta, Alistair T, Khan, Hameed, Walker, Susan, Gerrelli, Dianne, Wing, Kirsty, Bonaglia, Maria Clara, Giorda, Roberto, Berney, Tom, Mani, Elisa, Molteni, Massimo, Pinto, Dalila, Le Couteur, Ann, Hallmayer, Joachim, Sutcliffe, James S, Szatmari, Peter, Paterson, Andrew D, Scherer, Stephen W, Vieland, Veronica J, and Monaco, Anthony P

Published
2011
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