Genetics and Genomics Commons^™

The Plant Structure Ontology, A Unified Vocabulary Of Anatomy And Morphology Of A Flowering Plant, Katica Ilic, Elizabeth Kellogg, Pankaj Jaiswal, Felipe Zapata, Peter Stevens, Leszek Vincent, Shulamit Avraham, Leonore Reiser, Anuradha Pujar, Martin Sachs, Noah Whitman, Susan Mccouch, Mary Schaeffer, Doreen Ware, Lincoln Stein, Seung Rhee

Biology Department Faculty Works

Formal description of plant phenotypes and standardized annotation of gene expression and protein localization data require uniform terminology that accurately describes plant anatomy and morphology. This facilitates cross species comparative studies and quantitative comparison of phenotypes and expression patterns. A major drawback is variable terminology that is used to describe plant anatomy and morphology in publications and genomic databases for different species. The same terms are sometimes applied to different plant structures in different taxonomic groups. Conversely, similar structures are named by their species-specific terms. To address this problem, we created the Plant Structure Ontology (PSO), the first generic ontological …

The Plant Structure Ontology, A Unified Vocabulary Of Anatomy And Morphology Of A Flowering Plant, Katica Ilic, Elizabeth A. Kellogg, Pankaj Jaiswal, Felipe Zapata, Peter F. Stevens, Leszek P. Vincent, Shulamit Avraham, Leonore Reiser, Anuradha Pujar, Martin M. Sachs, Noah T. Whitman, Susan R. Mccouch, Mary L. Schaeffer, Doreen H. Ware, Lincoln D. Stein, Seung Y. Rhee

Peter Stevens

Caenorhabditis Briggsae Methods, Scott Everet Baird, Helen M. Chamberlin

Biological Sciences Faculty Publications

Caenorhabditis briggsae is being developed in parallel to C. elegans as a model system, primarily for the study of evolution. Like C. elegans, C. briggsae is a protandrous hermaphrodite and like C. elegans, its genome has been sequenced. From this point, these two model systems diverge. The development, behavior, and physiology of C. elegans have been characterized through tens of thousands of genetic and molecular studies. Genetic and molecular characterizations of C. briggsae are relatively few. Experimental resources in C. elegans include a high density recombination map that is well integrated with the genome sequence. The C. briggsae …

Use Of Hidden Markov Models For Qtl Mapping, Karl W. Broman

Johns Hopkins University, Dept. of Biostatistics Working Papers

An important aspect of the QTL mapping problem is the treatment of missing genotype data. If complete genotype data were available, QTL mapping would reduce to the problem of model selection in linear regression. However, in the consideration of loci in the intervals between the available genetic markers, genotype data is inherently missing. Even at the typed genetic markers, genotype data is seldom complete, as a result of failures in the genotyping assays or for the sake of economy (for example, in the case of selective genotyping, where only individuals with extreme phenotypes are genotyped). We discuss the use of …

A Sex-Linked Allele, Autosomal Modifiers And Temperature-Dependence Appear To Regulate Melanism In Male Mosquitofish (Gambusia Holbrooki), Lisa Horth

Biological Sciences Faculty Publications

About 1% of male mosquitofish (Gambusia holbrooki) express melanic (mottled-black) body coloration, which differs dramatically from the wild-type, silvery-gray coloration. Here, I report on the genetic inheritance pattern of melanic coloration, which indicates Y-linkage, and at least one autosomal modifier. Phenotypic expression of melanism is also affected by temperature. Expression is constitutive ( temperature insensitive) in some populations, inducible ( temperature sensitive) in others. Constitutive and inducible expression occur among geographically proximal populations. However, males from any single population demonstrate the same constitutive or inducible expression pattern as one another. The F1 males from inter-population crosses demonstrate temperature-related …

Genomeblast: A Web Tool For Small Genome Comparison, Guoqing Lu, Liying Jiang, Resa M. K. Helikar, Thaine W. Rowley, Luwen Zhang, Xianfeng Chen, Etsuko N. Moriyama

Biology Faculty Publications

Background: Comparative genomics has become an essential approach for identifying homologous gene candidates and their functions, and for studying genome evolution. There are many tools available for genome comparisons. Unfortunately, most of them are not applicable for the identification of unique genes and the inference of phylogenetic relationships in a given set of genomes.

Results: GenomeBlast is a Web tool developed for comparative analysis of multiple small genomes. A new parameter called "coverage" was introduced and used along with sequence identity to evaluate global similarity between genes. With GenomeBlast, the following results can be obtained: (1) unique genes in each …

Review Of "Plant Exploration For Longwood Gardens" By T. Aniśko, Nicholas J. Kaplinsky

Biology Faculty Works

No abstract provided.

The Qingdao Twin Registry: A Focus On Chronic Disease Research, C. Anderson Johnson, Zengchang Pang, Feng Ning, Jennifer B. Unger, Shaojie Wang, Qian Guo, Weihua Cao, Liming Lee

CGU Faculty Publications and Research

With the changing patterns of morbidity and mortality in China, noncommunicable chronic diseases have become the major threats to the health of the Chinese population. The causes of chronic diseases include genetic factors and behavioral risk factors such as the use of tobacco, alcohol, and other drugs, unhealthy dietary behaviors, and lack of physical activity. Twin studies offer a unique opportunity to disentangle the genetic and environmental risk and protective factors for chronic disease. The Qingdao Twin Registry (QTR) was initiated in 1998 as part of the National Chinese Twin Registry. Over 11,000 pairs of twins and multiples of all …

Wild And Aquaculture Populations Of The Eastern Oyster Compared Using Microsatellites, J Carlsson, Cl Morrison, Kimberly S. Reece

VIMS Articles

Five new microsatellite markers were developed for the eastern oyster (Crassostrea virginica), and allelic variability was compared between a wild Chesapeake Bay population (James River) and a hatchery strain (DEBY (TM)). All loci amplified readily and demonstrated allelic variability with the number of alleles ranging from 16 to 36 in the wild population and from 11 to 19 in the DEBY (TM) strain. Average observed and expected heterozygosities were estimated at 0.66 and 0.80 in the hatchery sample. The corresponding estimates were 0.91 and 0.75 in the wild sample. Results indicated lower genetic variability in the DEBY (TM) strain and …

An In Vitro Model Of Ovarian Cancer: Studying The Effects Of Talc And Pycnogenol®, Amber Renée Buz'zard

Loma Linda University Electronic Theses, Dissertations & Projects

Ovarian cancer is the sixth most common cancer and accounts for more deaths than any other cancer of the female reproductive system. The American Cancer Society has suggested that poor diet, talc and industrial pollutants may increase the risk of developing ovarian cancer. Talc is ubiquitous and concern is raised about its safety, role as a possible carcinogen and known ability to cause irritation and inflammation. Due to the silent nature of ovarian cancer, chemoprevention is a high priority. The most useful chemopreventive compounds will inhibit, delay or reverse carcinogenesis, and can be taken for long periods of time with …

Semiparametric Regression Of Multi-Dimensional Genetic Pathway Data: Least Squares Kernel Machines And Linear Mixed Models, Dawei Liu, Xihong Lin, Debashis Ghosh

Harvard University Biostatistics Working Paper Series

No abstract provided.

Limited Functional Redundancy And Oscillation Of Cyclins In Multinucleated Ashbya Gossypii Fungal Cells, A. Katrin Hungerbuehler, Peter Philippsen, Amy S. Gladfelter

Dartmouth Scholarship

Cyclin protein behavior has not been systematically investigated in multinucleated cells with asynchronous mitoses. Cyclins are canonical oscillating cell cycle proteins, but it is unclear how fluctuating protein gradients can be established in multinucleated cells where nuclei in different stages of the division cycle share the cytoplasm. Previous work in A. gossypii, a filamentous fungus in which nuclei divide asynchronously in a common cytoplasm, demonstrated that one G1 and one B-type cyclin do not fluctuate in abundance across the division cycle. We have undertaken a comprehensive analysis of all G1 and B-type cyclins in A. gossypii to determine whether …

Penalized Likelihood And Bayesian Methods For Sparse Contingency Tables: An Analysis Of Alternative Splicing In Full-Length Cdna Libraries, Corinne Dahinden, Giovanni Parmigiani, Mark C. Emerick, Peter Buhlmann

Johns Hopkins University, Dept. of Biostatistics Working Papers

We develop methods to perform model selection and parameter estimation in loglinear models for the analysis of sparse contingency tables to study the interaction of two or more factors. Typically, datasets arising from so-called full-length cDNA libraries, in the context of alternatively spliced genes, lead to such sparse contingency tables. Maximum Likelihood estimation of log-linear model coefficients fails to work because of zero cell entries. Therefore new methods are required to estimate the coefficients and to perform model selection. Our suggestions include computationally efficient penalization (Lasso-type) approaches as well as Bayesian methods using MCMC. We compare these procedures in a …

Multiple Testing With An Empirical Alternative Hypothesis, James E. Signorovitch

Harvard University Biostatistics Working Paper Series

An optimal multiple testing procedure is identified for linear hypotheses under the general linear model, maximizing the expected number of false null hypotheses rejected at any significance level. The optimal procedure depends on the unknown data-generating distribution, but can be consistently estimated. Drawing information together across many hypotheses, the estimated optimal procedure provides an empirical alternative hypothesis by adapting to underlying patterns of departure from the null. Proposed multiple testing procedures based on the empirical alternative are evaluated through simulations and an application to gene expression microarray data. Compared to a standard multiple testing procedure, it is not unusual for …

Prepms: Tof Ms Data Graphical Preprocessing Tool, Yuliya V. Karpievitch, Elizabeth G. Hill, Adam J. Smolka, Jeffrey S. Morris, Kevin R. Coombes, Keith A. Baggerly, Jonas S. Almeida

Jeffrey S. Morris

We introduce a simple-to-use graphical tool that enables researchers to easily prepare time-of-flight mass spectrometry data for analysis. For ease of use, the graphical executable provides default parameter settings experimentally determined to work well in most situations. These values can be changed by the user if desired. PrepMS is a stand-alone application made freely available (open source), and is under the General Public License (GPL). Its graphical user interface, default parameter settings, and display plots allow PrepMS to be used effectively for data preprocessing, peak detection, and visual data quality assessment.

The Allantois And Chorion, When Isolated Before Circulation Or Chorio-Allantoic Fusion, Have Hematopoietic Potential, Brandon M. Zeigler, Daisuke Sugiyama, Michael Chen, Yalin Guo, K. M. Downs, N. A. Speck

Dartmouth Scholarship

The chorio-allantoic placenta forms through the fusion of the allantois (progenitor tissue of the umbilical cord), with the chorionic plate. The murine placenta contains high levels of hematopoietic stem cells, and is therefore a stem cell niche. However, it is not known whether the placenta is a site of hematopoietic cell emergence, or whether hematopoietic cells originate from other sites in the conceptus and then colonize the placenta. Here, we show that the allantois and chorion, isolated prior to the establishment of circulation, have the potential to give rise to myeloid and definitive erythroid cells following explant culture. We further …

The Fat Cadherin Acts Through The Hippo Tumor-Suppressor Pathway To Regulate Tissue Size, Maria Willecke, Fisun Hamaratoglu, Madhuri Kango-Singh, Ryan Udan, Chiao-Lin Chen, Chunyao Tao, Xinwei Zhang, Georg Halder

Biology Faculty Publications

Background: The Hippo tumor-suppressor pathway has emerged as a key signaling pathway that controls tissue size in Drosophila. Merlin, the Drosophila homolog of the human Neurofibromatosis type-2 (NF2) tumor-suppressor gene, and the related protein Expanded are the most upstream components of the Hippo pathway identified so far. However, components acting upstream of Expanded and Merlin, such as transmembrane receptors, have not yet been identified.

Results: Here, we report that the protocadherin Fat acts as an upstream component in the Hippo pathway. Fat is a known tumor-suppressor gene in Drosophila, and fat mutants have severely overgrown imaginal discs. We …

Lobe And Serrate Are Required For Cell Survival During Early Eye Development In Drosophila, Amit Singh, Xiao Shi, Kwang-Wook Choi

Biology Faculty Publications

Organogenesis involves an initial surge of cell proliferation, leading to differentiation. This is followed by cell death in order to remove extra cells. During early development, there is little or no cell death. However, there is a lack of information concerning the genes required for survival during the early cell-proliferation phase. Here, we show that Lobe (L) and the Notch (N) ligand Serrate (Ser), which are both involved in ventral eye growth, are required for cell survival in the early eye disc. We observed that the loss-of-ventral-eye phenotype in L or Ser mutants is due to …

Validity, Identification, And Distribution Of The Roundscale Spearfish, Tetrapturus Georgii (Teleostei: Istiophoridae): Morphological And Molecular Evidence, Mahmood S. Shivji, Jennifer E. Magnussen, Lawrence R. Beerkircher, George Hinteregger, Dennis W. Lee, Joseph E. Serafy, Eric D. Prince

Marine & Environmental Sciences Faculty Articles

The roundscale spearfish, Tetrapturus georgii Lowe, 1840, is known only from four specimens from the Mediterranean and eastern North Atlantic. Additional specimens have not been identified since 1961, making the validity and distribution of this species unclear. Analysis of 16 billfish specimens from the western North Atlantic on the basis of scale morphology, anus position, and mitochondrial DNA confirms the validity of this species and extends its distribution. Mid-lateral scales are soft, notably rounded anteriorly, and bear 2–3 points distinct from those of the sympatric longbill spearfish (Tetrapturus pfluegeri Robins and de Sylva, 1963) and white marlin (Tetrapturus …

Genetic Analysis Of White Marlin (Tetrapturus Albidus) Stock Structure, John Graves, Jan Mcdowell

VIMS Articles

The genetic basis of stock structure of white marlin (Tetrapturus albidus Poey, 1860) was inferred from analyses of five tetranucleotide repeat microsatellite loci (n = 214) and the mitochondrial (mt)DNA control region (n = 99) of white marlin from four geographic regions in the Atlantic Ocean. Considerable genetic variation was present in all collections for all molecular markers. Analysis of replicate collections taken in different years from three regions revealed no significant differences in the distribution of allele frequencies among years within regions. The value of global F-statistics for both multilocus microsatellite data and mtDNA control region sequences approached significance …

Nonparametric Pathway-Based Regression Models For Analysis Of Genomic Data, Zhi Wei, Hongzhe Li

Hongzhe Li

High-throughout genomic data provide an opportunity for identifying pathways and genes that are related to various clinical phenotypes. Besides these genomic data, another valuable source of data is the biological knowledge about genes and pathways that might be related to the phenotypes of many complex diseases. Databases of such knowledge are often called the metadata. In microarray data analysis, such metadata are currently explored in post hoc ways by gene set enrichment analysis but have hardly been utilized in the modeling step. We propose to develop and evaluate a pathway-based gradient descent boosting procedure for nonparametric pathways-based regression(NPR) analysis to …

Group Additive Regression Models For Genomic Data Analysis, Yihui Luan, Hongzhe Li

Hongzhe Li

One important problem in genomic research is to identify genomic features such as gene expression data or DNA single nucleotide polymorphisms (SNPs) that are related to clinical phenotypes. Often these genomic data can be naturally divided into biologically meaningful groups such as genes belonging to the same pathways or SNPs within genes. In this paper, we propose group additive regression models and a group gradient descent boosting procedure for identifying groups of genomic features that are related to clinical phenotypes. Our simulation results show that by dividing the variables into appropriate groups, we can obtain better identification of the group …

Estimating Genome-Wide Copy Number Using Allele Specific Mixture Models, Wenyi Wang , Benilton Caravalho, Nate Miller, Jonathan Pevsner, Aravinda Chakravarti, Rafael A. Irizarry

Johns Hopkins University, Dept. of Biostatistics Working Papers

Genomic changes such as copy number alterations are thought to be one of the major underlying causes of human phenotypic variation among normal and disease subjects [23,11,25,26,5,4,7,18]. These include chromosomal regions with so-called copy number alterations: instead of the expected two copies, a section of the chromosome for a particular individual may have zero copies (homozygous deletion), one copy (hemizygous deletions), or more than two copies (amplifications). The canonical example is Down syndrome which is caused by an extra copy of chromosome 21. Identification of such abnormalities in smaller regions has been of great interest, because it is believed to …

The Role Of Mapks In B Cell Receptor-Induced Down-Regulation Of Egr-1 In Immature B Lymphoma Cells, Jiyuan Ke, Murali Gururajan, Anupam Kumar, Alan Simmons, Lilia Turcios, Ralph Lakshman Chelvarajan, David M. Cohen, David L. Wiest, John G. Monroe, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Cross-linking of the B cell receptor (BCR) on the immature B lymphoma cell line BKS-2 induces growth inhibition and apoptosis accompanied by rapid down-regulation of the immediate-early gene egr-1. In these lymphoma cells, egr-1 is expressed constitutively and has a prosurvival role, as Egr-1-specific antisense oligonucleotides or expression of a dominant-negative inhibitor of Egr-1 also prevented the growth of BKS-2 cells. Moreover, enhancement of Egr-1 protein with phorbol 12-myristate 13-acetate or an egr-1 expression vector rescued BKS-2 cells from BCR signal-induced growth inhibition. Nuclear run-on and mRNA stability assays indicated that BCR-derived signals act at the transcriptional level to …

Analysis And Functional Annotation Of Expressed Sequence Tags From The Fall Armyworm Spodoptera Frugiperda, Youping Deng, Yinghua Dong, Venkata Thodima, Rollie J. Clem, A. Lorena Passareli

Faculty Publications

Background

Little is known about the genome sequences of lepidopteran insects, although this group of insects has been studied extensively in the fields of endocrinology, development, immunity, and pathogen-host interactions. In addition, cell lines derived from Spodoptera frugiperda and other lepidopteran insects are routinely used for baculovirus foreign gene expression. This study reports the results of an expressed sequence tag (EST) sequencing project in cells from the lepidopteran insect S. frugiperda, the fall armyworm.

Results

We have constructed an EST database using two cDNA libraries from the S. frugiperda-derived cell line, SF-21. The database consists of 2,367 ESTs …

Exploration Of Distributional Models For A Novel Intensity-Dependent Normalization , Nicola Lama, Patrizia Boracchi, Elia Mario Biganzoli

COBRA Preprint Series

Currently used gene intensity-dependent normalization methods, based on regression smoothing techniques, usually approach the two problems of location bias detrending and data re-scaling without taking into account the censoring characteristic of certain gene expressions produced by experiment measurement constraints or by previous normalization steps. Moreover, the bias vs variance balance control of normalization procedures is not often discussed but left to the user's experience. Here an approximate maximum likelihood procedure to fit a model smoothing the dependences of log-fold gene expression differences on average gene intensities is presented. Central tendency and scaling factor were modeled by means of B-splines smoothing …

Distance-Based Genome Rearrangement Phylogeny, Li-San Wang, Tandy Warnow, Bernard M.E. Moret, Robert K. Jansen, Linda A. Raubeson

All Faculty Scholarship for the College of the Sciences

Evolution operates on whole genomes through direct rearrangements of genes, such as inversions, transpositions, and inverted transpositions, as well as through operations, such as duplications, losses, and transfers, that also affect the gene content of the genomes. Because these events are rare relative to nucleotide substitutions, gene order data offer the possibility of resolving ancient branches in the tree of life; the combination of gene order data with sequence data also has the potential to provide more robust phylogenetic reconstructions, since each can elucidate evolution at different time scales. Distance corrections greatly improve the accuracy of phylogeny reconstructions from DNA …

Mig-5/Dsh Controls Cell Fate Determination And Cell Migration In C. Elegans, Timothy Walston, Chaobo Guo, Rui Proenca, Mingfu Wu, Michael Herman, Jeff Hardin, Edward Hedgecock

School of Biological Sciences: Faculty Publications

Cell fate determination and cell migration are two essential events in the development of an organism. We identify mig-5, a Dishevelled family member, as a gene that regulates several cell fate decisions and cell migrations that are important during C. elegans embryonic and larval development. In offspring from mig-5 mutants, cell migrations are defective during hypodermal morphogenesis, QL neuroblast migration, and the gonad arm migration led by the distal tip cells (DTCs). In addition to abnormal migration, DTC fate is affected, resulting in either an absent or an extra DTC. The cell fates of the anchor cell in hermaphrodites …

A Unifying Approach For Haplotype Analysis Of Quantitative Traits In Family-Based Association Studies: Testing And Estimating Gene-Environment Interactions With Complex Exposure Variables, Stijn Vansteelandt, Christoph Lange

COBRA Preprint Series

We propose robust and e±cient tests and estimators for gene-environment/gene-drug interactions in family-based association studies. The methodology is designed for studies in which haplotypes, quantitative pheno- types and complex exposure/treatment variables are analyzed. Using causal inference methodology, we derive family-based association tests and estimators for the genetic main effects and the interactions. The tests and estimators are robust against population admixture and strati¯cation without requiring adjustment for confounding variables. We illustrate the practical relevance of our approach by an application to a COPD study. The data analysis suggests a gene-environment interaction between a SNP in the Serpine gene and smok- …

Secondary Metabolic Gene Cluster Silencing In Aspergillus Nidulans, J. W. Bok, D. Noordermeer, Shubha Kale Ireland, N. P. Keller

Faculty and Staff Publications

In contrast to most primary metabolism genes, the genes involved in secondary metabolism and certain nutrient utilization pathways are clustered in fungi. Recently a nuclear protein, LaeA, was found to be required for the transcription of several secondary metabolite gene clusters in Aspergillus nidulans. Here we show that LaeA regulation does not extend to nutrient utilization or the spoC1 sporulation clusters. One of the secondary metabolite clusters regulated by LaeA contains the positive regulatory (i.e. aflR) and biosynthetic genes required for biosynthesis of sterigmatocystin (ST), a carcinogenic toxin. Analysis of ST gene cluster expression indicates LaeA regulation of the cluster …