Genetics and Genomics Commons^™

Estimation In Semiparametric Transition Measurement Error Models For Longitudinal Data, Wenqin Pan, Donglin Zeng, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Nonparametric Regression Using Local Kernel Estimating Equations For Correlated Failure Time Data, Zhangsheng Yu, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Causal Inference In Hybrid Intervention Trials Involving Treatment Choice, Qi Long, Rod Little, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Comparison Of Methods For Estimating The Causal Effect Of A Treatment In Randomized Clinical Trials Subject To Noncompliance, Rod Little, Qi Long, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Gene Order Data From A Model Amphibian (Ambystoma): New Perspectives On Vertebrate Genome Structure And Evolution, Jeramiah J. Smith, S. Randal Voss

Biology Faculty Publications

BACKGROUND: Because amphibians arise from a branch of the vertebrate evolutionary tree that is juxtaposed between fishes and amniotes, they provide important comparative perspective for reconstructing character changes that have occurred during vertebrate evolution. Here, we report the first comparative study of vertebrate genome structure that includes a representative amphibian. We used 491 transcribed sequences from a salamander (Ambystoma) genetic map and whole genome assemblies for human, mouse, rat, dog, chicken, zebrafish, and the freshwater pufferfish Tetraodon nigroviridis to compare gene orders and rearrangement rates.

RESULTS: Ambystoma has experienced a rate of genome rearrangement that is substantially lower than mammalian …

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

UPenn Biostatistics Working Papers

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 …

Kir/Hla Pleiotropism: Protection Against Both Hiv And Opportunistic Infections, Ying Qi, Maureen P. Martin, Xiaojiang Gao, Lisa Jacobson, James J. Goedert, Susan Buchbinder, Gregory D. Kirk, Stephen J. O'Brien, John Trowsdale, Mary Carrington

Biology Faculty Articles

The compound genotype KIR3DS1/HLA-B Bw4-80I, which presumably favors natural killer cell activation, has been implicated in protection against HIV disease. We show that this genotype confers dual protection over the course of HIV disease; early direct containment of HIV viral load, and late specific defense against opportunistic infections, but not AIDS-related malignancies. The double protection of KIR3DS1/Bw4-80I in an etiologically complex disease such as AIDS, along with the disease specificity of its effects is conceptually novel and underscores the intricacy of host immunogenetics against HIV/AIDS.

Extensions To Gene Set Enrichment, Zhen Jiang, Robert Gentleman

Bioconductor Project Working Papers

Motivation: Gene Set Enrichment Analysis (GSEA) has been developed recently to capture moderate but coordinated changes in the expression of sets of functionally related genes. We propose number of extensions to GSEA, which uses different statistics to describe the association between genes and phenotype of interest. We make use of dimension reduction procedures, such as principle component analysis to identify gene sets containing coordinated genes. We also address the problem of overlapping among gene sets in this paper.

Results: We applied our methods to the data come from a clinical trial in acute lymphoblastic leukemia (ALL) [1]. We identified interesting …

Chironomid Hemoglobin Genetic Diversity As An Indicator Of The New Jersey Hackensack Meadowlands Wetland Health, Lene Marie De Coursin Jacobs

Seton Hall University Dissertations and Theses (ETDs)

Kearny Marsh located within the Hackensack Meadowlands is a freshwater wetland impacted by multiple environmental stressors from human activity. The marsh is located in the northeastern New Jersey metropolitan area. Chironomid larvae, aquatic larvae of midge fly, were analyzed from two Kearny Marsh sample sites, W9 and W22. A previous sediment analysis and toxicity study characterized heavy metal contaminants the marsh. The data results were applied in this thesis study to determine the correlation between environmental stressors and chironomid genetic diversity. Site W9 sediment was impacted by severe levels of total heavy metal contamination, whereas site W22 had just below …

Circadian Rhythmicity By Autocatalysis, Arun Mehra, Christian I. Hong, Mi Shi, Jennifer J. Loros, Jay C. Dunlap, Peter Ruoff

Dartmouth Scholarship

The temperature compensated in vitro oscillation of cyanobacterial KaiC phosphorylation, the first example of a thermodynamically closed system showing circadian rhythmicity, only involves the three Kai proteins (KaiA, KaiB, and KaiC) and ATP. In this paper, we describe a model in which the KaiA- and KaiB-assisted autocatalytic phosphorylation and dephosphorylation of KaiC are the source for circadian rhythmicity. This model, based upon autocatalysis instead of transcription-translation negative feedback, shows temperature-compensated circadian limit-cycle oscillations with KaiC phosphorylation profiles and has period lengths and rate constant values that are consistent with experimental observations.

Fdr And Bayesian Multiple Comparisons Rules, Peter Muller, Giovanni Parmigiani, Kenneth Rice

Johns Hopkins University, Dept. of Biostatistics Working Papers

We discuss Bayesian approaches to multiple comparison problems, using a decision theoretic perspective to critically compare competing approaches. We set up decision problems that lead to the use of FDR-based rules and generalizations. Alternative definitions of the probability model and the utility function lead to different rules and problem-specific adjustments. Using a loss function that controls realized FDR we derive an optimal Bayes rule that is a variation of the Benjamini and Hochberg (1995) procedure. The cutoff is based on increments in ordered posterior probabilities instead of ordered p- values. Throughout the discussion we take a Bayesian perspective. In particular, …

Environmental Stress And Reproduction In Drosophila Melanogaster: Starvation Resistance, Ovariole Numbers And Early Age Egg Production, Marta L. Wayne, Usha Soundararajan, Lawrence G. Harshman

Papers in Genetics

Background: The Y model of resource allocation predicts a tradeoff between reproduction and survival. Environmental stress could affect a tradeoff between reproduction and survival, but the physiological mechanisms underlying environmental mediation of the tradeoff are largely unknown. One example is the tradeoff between starvation resistance and early fecundity. One goal of the present study was to determine if reduced early age fecundity was indeed a robust indirect response to selection for starvation resistance, by investigation of a set of D. melanogaster starvation selected lines which had not previously been characterized for age specific egg production. Another goal of the present …

A Subset Of Arabidopsis Ap2 Transcription Factors Mediates Cytokinin Responses In Concert With A Two-Component Pathway, Aaron M. Rashotte, Michael G. Mason, Claire E. Hutchison, Fernando J. Ferreira, G. Eric Schaller, Joseph J. Kieber

Dartmouth Scholarship

The plant hormone cytokinin regulates numerous growth and developmental processes. A signal transduction pathway for cytokinin has been elucidated that is similar to bacterial two-component phosphorelays. In Arabidopsis, this pathway is comprised of receptors that are similar to sensor histidine kinases, histidine-containing phosphotransfer proteins, and response regulators (ARRs). There are two classes of response regulators, the type-A ARRs, which act as negative regulators of cytokinin responses, and the type-B ARRs, which are transcription factors that play a positive role in mediating cytokinin-regulated gene expression. Here we show that several closely related members of the Arabidopsis AP2 gene family of …

Consistent Effects Of Tsg101 Genetic Variability On Multiple Outcomes Of Exposure To Human Immunodeficiency Virus Type 1, Arman A. Bashirova, Gabriela Bleiber, Ying Qi, Holli Hutcheson, Traci Yamashita, Randall C. Johnson, Jie Cheng, Galit Alter, James J. Goedert, Susan Buchbinder, Keith Hoots, David Vlahov, Margaret May, Frank Maldarelli, Lisa Jacobson, Stephen J. O'Brien, Amalio Telenti, Mary Carrington

Biology Faculty Articles

Tumor susceptibility gene 101 (TSG101) encodes a host cellular protein that is appropriated by human immunodeficiency virus type 1 (HIV-1) in the budding process of viral particles from infected cells. Variation in the coding or noncoding regions of the gene could potentially affect the degree of TSG101-mediated release of viral particles. While the coding regions of the gene were found to lack nonsynonymous variants, two polymorphic sites in the TSG101 5' area were identified that were associated with the rate of AIDS progression among Caucasians. These single-nucleotide polymorphisms (SNPs), located at positions -183 and +181 relative to the …

Sheep Updates 2006 - Part 2, Darryl Smith, Kathryn Kemper, David Rutley, R. R. Woolaston, D. J. Brown, K. D. Atkins, A. E. Casey, A. J. Ball, David Hopkins, David Stanley, Leonie Martin, Arthur Gilmour, Remy Van De Ven, Geoff Duddy, Steve Semple, David Kessell, Andrew Thompson

Sheep Updates

This session covers six papers from different authors:

GENETICS

1. Novel selection traits - what are the possible side effects?, Darryl Smith, Kathryn Kemper, South Australian Research and Development Institute, David Rutley, University of Adelaide.

2. Genetic Changes in the Australian Merino since 1900, Sheep Genetics Australia Technical Committee, R.R. Woolaston Pullenvale, Queensland, D.J. Brown, Animal Genetics and Breeding Unit*, University of New England, K.D. Atkins, A.E. Casey, NSW Department of Primary Industries, A.J. Ball, Meat and Livestock Australia, University of New England

3. Influence of Sire Growth Estimated Breeding Value (EBV0 on Progeny Growth, David Hopkins, David Stanley, Leonie …

Exploration, Normalization, And Genotype Calls Of High Density Oligonucleotide Snp Array Data, Benilton Carvalho, Terence P. Speed, Rafael A. Irizarry

Johns Hopkins University, Dept. of Biostatistics Working Papers

In most microarray technologies, a number of critical steps are required to convert raw intensity measurements into the data relied upon by data analysts, biologists and clinicians. These data manipulations, referred to as preprocessing, can influence the quality of the ultimate measurements. In the last few years, the high-throughput measurement of gene expression is the most popular application of microarray technology. For this application, various groups have demonstrated that the use of modern statistical methodology can substantially improve accuracy and precision of gene expression measurements, relative to ad-hoc procedures introduced by designers and manufacturers of the technology. Currently, other applications …

Coordinated Diabrotica Genetics Research: Accelerating Progress On An Urgent Insect Pest Problem, Thomas W. Sappington, Blair D. Siegfried, Thomas Guillemaud

Department of Entomology: Faculty Publications

Diabrotica spp. (western, northern, and Mexican corn rootworms) represent the main pest complex of continuous field corn, Zea mays (L.), in North America. The western corn rootworm, Diabrotica virgifera virgifera LeConte, also has become the main pest of continuous corn in Central and Southeastern Europe since its introduction near Belgrade 15–20 years ago, and it represents a major risk to Western Europe. It has already caused economic losses in Eastern Europe, and Western countries such as France have committed large expenditures for containment and/or eradication.

Rootworm larvae feed on corn roots, and damaged plants are more susceptible to drought and …

Cross-Subtype T-Cell Immune Responses Induced By A Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen†0--, Eric A. Weaver, Zhongjing Lu, Zenaido T. Camacho, Fatiha Moukdar, Hua-Xin Liao, Ben-Jiang Ma, Mark Muldoon, James Theiler, Gary J. Nabel, Norman L. Letvin, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes, Feng Gao

Nebraska Center for Virology: Faculty Publications

The genetic diversity among globally circulating human immunodeficiency virus type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have generated a synthetic groupMconsensus env gene (CON6) for induction of cross-subtype immune responses and report here a comparative study of T-cell responses to this and natural strain env immunogens in a murine model. Three different strains of mice were immunized with CON6 as well as subtype A, B, or C env immunogens, using a DNA prime-recombinant vaccinia virus boost strategy. T-cell epitopes were mapped by gamma interferon enzyme-linked immunospot analysis using five overlapping Env peptide sets from …

Saccharomyces Cerevisiae-Based Molecular Tool Kit For Manipulation Of Genes From Gram-Negative Bacteria, Robert M. Q. Shanks, Nicky C. Caiazza, Shannon M. Hinsa, Christine M. Toutain, George A. O'Toole

Dartmouth Scholarship

A tool kit of vectors was designed to manipulate and express genes from a wide range of gram-negative species by using in vivo recombination. Saccharomyces cerevisiae can use its native recombination proteins to combine several amplicons in a single transformation step with high efficiency. We show that this technology is particularly useful for vector design. Shuttle, suicide, and expression vectors useful in a diverse group of bacteria are described and utilized. This report describes the use of these vectors to mutate clpX and clpP of the opportunistic pathogen Pseudomonas aeruginosa and to explore their roles in biofilm formation and surface …

Multivariate Analysis And Visualization Of Splicing Correlations In Single-Gene Transcriptomes, Mark C. Emerick, Giovanni Parmigiani, William S. Agnew

Johns Hopkins University, Dept. of Biostatistics Working Papers

Through ‘combinatorial splicing’, RNA metabolism may create enormous structural diversity in the proteome. Functional interactions among multiple alternative domains can have a disproportionate impact on the phenotype, requiring integrated RNA-level regulation of molecular composition. Splicing correlations within molecules expressed from a single gene, where these effects would be greatest, provide valuable clues to functional relationships and targets for splicing regulation. We present tools to visualize complex splicing patterns in full-length cDNA libraries. Developmental changes in pair-wise correlations are presented vectorially in ‘clock plots’ and linkage grids. Higher-order correlations are assessed via a loglinear model and Monte Carlo analysis with an …

A Faster Circular Binary Segmentation Algorithm For The Analysis Of Array Cgh Data, E S. Venkatraman, Adam Olshen

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

Motivation: Array CGH technologies enable the simultaneous measurement of DNA copy number for thousands of sites on a genome. We developed the circular binary segmentation (CBS) algorithm to divide the genome into regions of equal copy number (Olshen {\it et~al}, 2004). The algorithm tests for change-points using a maximal $t$-statistic with a permutation reference distribution to obtain the corresponding $p$-value. The number of computations required for the maximal test statistic is $O(N^2),$ where $N$ is the number of markers. This makes the full permutation approach computationally prohibitive for the newer arrays that contain tens of thousands markers and highlights the …

Plasq: A Generalized Linear Model-Based Procedure To Determine Allelic Dosage Ini Cancer Cells From Snp Array Data, Thomas Laframboise, David P. Harrington, Barbara A. Weir

Harvard University Biostatistics Working Paper Series

No abstract provided.

Genetic Factors Leading To Chronic Epstein–Barr Virus Infection And Nasopharyngeal Carcinoma In South East China: Study Design, Methods And Feasibility, Xiu Chan Guo, Kevin Scott, Yan Liu, Michael Dean, Victor David, George W. Nelson, Randall C. Johnson, Holli H. Dilks, J. A. Lautenberger, Bailey Kessing, Janice S. Martenson, Li Guan, Shan Sun, Hong Deng, Yuming Zheng, Guy De The, Jian Liao, Yi Zeng, Stephen J. O'Brien, Cheryl Winkler

Biology Faculty Articles

Nasopharyngeal carcinoma (NPC) is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of genetic factors involved in the development of chronic Epstein-Barr virus infection and NPC remains elusive, however. Here, we describe a two-phase, population-based, case-control study of Han Chinese from Guangxi province, where the NPC incidence rate rises to a high of 25-50 per 100,000 individuals. Phase I, powered to detect single gene associations, enrolled 984 subjects to determine feasibility, to develop infrastructure and logistics and to determine error rates in sample …

Membrane Organization And Multimeric Interactions Of The Aer Receptor In E. Coli, Divya Dashrathkumar Amin

Loma Linda University Electronic Theses, Dissertations & Projects

Escherichia coli swims toward niches ideal for generating maximum energy by monitoring the environment with the aerotaxis sensor, Aer. This receptor has an N-terminal PAS domain, which is a sensor module present in a variety of proteins from all kingdoms of life (including humans). To date, the mechanism of signaling from a PAS sensor domain to a single signaling receiver domain has not been resolved. In Aer, the PAS sensor is separated from the signaling region by a membrane anchor. Most "transmembrane prediction" programs forecast a single membrane span for this membrane anchor, but such a topology is inconsistent our …

Effects Of Ultraviolet-B Radiation On Leaf Morphology Of Arabidopsis Thaliana (L.) Heynh. (Brassicaceae), Maria Regina Torres Boeger, Mary E. Poulson

Biology Faculty Scholarship

Reduction of the ozone layer results in the increase in ultraviolet radiation reaching the earth's surface, especially the ultraviolet-B (UV-B). The increase of radiation may induce structural and physiological changes in plants, influencing their growth and development. This paper evaluates the effects of ambient UV-B radiation upon to the leaf morphology of Arabidopsis thaliana developed under controlled conditions. The seeds of A. thaliana grown in environmental chamber, with 300 µmol m^-2s^-1 de photosynthetically active radiation (PAR) with and without 6 kJ m^-2 s^-1 of radiation UV-B_be (UV-B_be; UV-B biologically effective). After 21 …

Desulfovibrio Desulfuricans G20 Tetraheme Cytochrome Structure At 1.5 A˚ And Cytochrome Interaction With Metal Complexes, Mrunalini Pattarkine, J J. Tanner, C A. Bottoms, Y H. Lee, Judy D. Wall

Faculty Works

The structure of the type I tetraheme cytochrome c3 from Desulfovibrio desulfuricans G20 was determined to 1.5 A˚ by X-ray crystallography. In addition to the oxidized form, the structure of the molybdate-bound form of the protein was determined from oxidized crystals soaked in sodium molybdate. Only small structural shifts were obtained with metal binding, consistent with the remarkable structural stability of this protein. In vitro experiments with pure cytochrome showed that molybdate could oxidize the reduced cytochrome, although not as rapidly as U(VI) present as uranyl acetate. Alterations in the overall conformation and thermostability of the metal-oxidized protein were investigated …

Bounded Search For De Novo Identification Of Degenerate Cis-Regulatory Elements, Jonathan M. Carlson, Arijit Chakravarty, Radhika S. Khetani, Robert H. Gross

Dartmouth Scholarship

The identification of statistically overrepresented sequences in the upstream regions of coregulated genes should theoretically permit the identification of potential cis-regulatory elements. However, in practice many cis-regulatory elements are highly degenerate, precluding the use of an exhaustive word-counting strategy for their identification. While numerous methods exist for inferring base distributions using a position weight matrix, recent studies suggest that the independence assumptions inherent in the model, as well as the inability to reach a global optimum, limit this approach.

Cloning And Overexpression Of Imp/Osta, An Essential Escherichia Coli Outer Membrane Protein With A Possible Role In Lipid Transport, Leslie Lekatz

Honors Capstones

Capstone submitted as a graduation requirement for the BSU Honors Program.

In Vitro Expression And Purification Of Class I Mhc Molecules, Loi Cheng

Honors Scholar Theses

The major histocompatibility complex (MHC) is a gene family responsible for many critical functions of the immune system in most vertebrates. The MHC consists of three classes differentiated by their structure and function, and MHC class I encodes antigen binding proteins as well as chaperone and accessory proteins such as tapasin. The purpose of this project is to reconstitute several human MHC class I molecules in their peptide-filled and peptide-deficient forms, and to purify these proteins for biochemical study. The expressed proteins include wild type and mutant variants of the fusion protein human leukocyte antigen HLA-B*0801-fos, and human beta-2-microglobulin (β2m). …

Analysis Of Distal-Less Gene Expression In Ciona Intestinalis, Michelle Cangiano

Senior Honors Projects

Several homeobox-containing genes related to Distal-less (Dlx/Dll) have been isolated from a wide variety of organisms and have been shown to function as developmental regulators. In Drosophila only one Distal-less gene has been identified so far, and in vertebrates many components of the Distal-less family have been characterized. This suggests that, during the evolution of the Chordate phylum, the Dlx genes arose from an ancestral Distal-less gene via gene duplication. Three Dll homeoboxes have been isolated from the protochordate Ciona intestinalis and their clustered arrangement has been described. Since Ciona is regarded as one of the most primitive extant chordates, …