Genetics and Genomics Commons^™

Classification Using Generalized Partial Least Squares, Beiying Ding, Robert Gentleman

Bioconductor Project Working Papers

The advances in computational biology have made simultaneous monitoring of thousands of features possible. The high throughput technologies not only bring about a much richer information context in which to study various aspects of gene functions but they also present challenge of analyzing data with large number of covariates and few samples. As an integral part of machine learning, classification of samples into two or more categories is almost always of interest to scientists. In this paper, we address the question of classification in this setting by extending partial least squares (PLS), a popular dimension reduction tool in chemometrics, in …

Conversion Of Myoblasts To Physiologically Active Neuronal Phenotype, Yumi Watanabe, Sei Kameoka, Vidya Gopalakrishnan, Kenneth D Aldape, Zhizhong Z Pan, Frederick F Lang, Sadhan Majumder

Faculty, Staff and Student Publications

Repressor element 1 (RE1)-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) can repress several terminal neuronal differentiation genes by binding to a specific DNA sequence (RE1/neuron-restrictive silencer element [NRSE]) present in their regulatory regions. REST-VP16 binds to the same RE1/NRSE, but activates these REST/NRSF target genes. However, it is unclear whether REST-VP16 expression is sufficient to cause formation of functional neurons either from neural stem cells or from heterologous stem cells. Here we show that the expression of REST-VP16 in myoblasts grown under muscle differentiation conditions blocked entry into the muscle differentiation pathway, countered endogenous REST/NRSF-dependent repression, activated the REST/NRSF target …

The C. Elegans Heterochronic Gene Lin-46 Affects Developmental Timing At Two Larval Stages And Encodes A Relative Of The Scaffolding Protein Gephyrin, A. S.-R. Pepper, Jill E. Mccane, Kevin Kemper, Dennis Au Yeung, Rosalind C. Lee, Victor Ambros, Eric G. Moss

Dartmouth Scholarship

The succession of developmental events in the C. elegans larva is governed by the heterochronic genes. When mutated, these genes cause either precocious or retarded developmental phenotypes, in which stage-specific patterns of cell division and differentiation are either skipped or reiterated, respectively. We identified a new heterochronic gene, lin-46, from mutations that suppress the precocious phenotypes caused by mutations in the heterochronic genes lin-14 and lin-28. lin-46 mutants on their own display retarded phenotypes in which cell division patterns are reiterated and differentiation is prevented in certain cell lineages. Our analysis indicates that lin-46 acts at a step immediately downstream …

Patterns Of Feline Immunodeficiency Virus Multiple Infection And Genome Divergence In A Free-Ranging Population Of African Lions, Jennifer L. Troyer, Jill Pecon-Slattery, Melody E. Roelke, Lori Black, Craig Packer, Stephen J. O'Brien

Biology Faculty Articles

Feline immunodeficiency virus (FIV) is a lentivirus that causes AIDS-like immunodeficiency disease in domestic cats. Free-ranging lions, Panthera leo, carry a chronic species-specific strain of FIV, FIV-Ple, which so far has not been convincingly connected with immune pathology or mortality. FIV-Ple, harboring the three distinct strains A, B, and C defined by pol gene sequence divergences, is endemic in the large outbred population of lions in the Serengeti ecosystem in Tanzania. Here we describe the pattern of variation in the three FIV genes gag, pol-RT, and pol-RNase among lions within 13 prides to assess the occurrence of FIV infection and …

Inheritance Of Trunk Banding In The Tetra (Gymnocorymbus Ternetzi Characidae), Jack Frankel

Department of Biology Faculty Publications

The tetra (Gymnocorymbus ternetzi) exhibits two phenotypes associated with trunk banding. Fish possess either a smoky-gray coloration with two prominent black vertical bands located directly behind the operculum (black tetra) or a lighter coloration and lack these bands (white skirt tetra). Segregation patterns observed from the progenies of 11 different crosses suggest that the inheritance of these phenotypes is controlled by two autosomal loci acting in a complementary fashion, with dominance at both loci required for the expression of the darker, banded phenotype.

Genomically Intact Endogenous Feline Leukemia Viruses Of Recent Origin, Alfred L. Roca, Jill Pecon-Slattery, Stephen J. O'Brien

Biology Faculty Articles

We isolated and sequenced two complete endogenous feline leukemia viruses (enFeLVs), designated enFeLV-AGTT and enFeLV-GGAG. In enFeLV-AGTT, the open reading frames are reminiscent of a functioning FeLV genome, and the 5′ and 3′ long terminal repeat sequences are identical. Neither endogenous provirus is genetically fixed in cats but polymorphic, with 8.9 and 15.2% prevalence for enFeLV-AGTT and enFeLV-GGAG, respectively, among a survey of domestic cats. Neither provirus was found in the genomes of related species of the Felis genus, previously shown to harbor enFeLVs. The absence of mutational divergence, polymorphic incidence in cats, and absence in related species suggest that …

Drosophila As An Emerging Model To Study Metastasis, Madhuri Kango-Singh, Georg Halder

Biology Faculty Publications

Metastasis is the primary cause of human cancer-related deaths. Two recent studies describe a system for testing how multiple genetic events synergize to promote neoplastic growth and metastasis in Drosophila, paving the way for systematic approaches to understanding metastasis using the powerful tools of Drosophila genetics.

Federal Court Adjudication Of State Prisoner Claims For Post-Conviction Dna Testing: A Bifurcated Approach, Dylan Ruga

The University of New Hampshire Law Review

[Excerpt] “Undoubtedly, there are innocent people in prison. Moreover, it is probable that the wrongly convicted, if given a chance to conduct DNA testing on evidence used against them at trial, could establish their innocence. […]

Part II of this Comment will examine the reasoning behind recent circuit court decisions concerning prisoners’ rights to post-conviction genetic testing. I will explain that a bifurcated approach is the appropriate paradigm for reviewing these claims and demonstrate why three of the four circuit courts erred in their analyses. This part also will review the Supreme Court decisions cited by the circuit courts and …

A Transgenic Marker For Newly Born Granule Cells In Dentate Gyrus, Linda S. Overstreet, Shane T. Hentges, Viviana F. Bumaschny, Flavio S.J. De Souza, James L. Smart, Andrea M. Santangelo, Malcolm J. Low, Gary L. Westbrook, Marcelo Rubinstein

Faculty Publications - Department of Biological & Molecular Science

Neurogenesis in the dentate gyrus continues into adulthood, yet little is known about the function of newly born neurons or how they integrate into an existing network of mature neurons. We made transgenic mice that selectively and transiently express enhanced green fluorescent protein (EGFP) in newly born granule cells of the dentate gyrus under the transcriptional control of proopiomelanocortin (POMC) genomic sequences. Analysis of transgenic pedigrees with truncation or deletion mutations indicated that EGFP expression in the dentate gyrus required cryptic POMC promoter regions dispensable for arcuate hypothalamic or pituitary expression. Unlike arcuate neurons, dentate granule cells did not express …

Seroprevalence Of Bartonella Infection In American Free-Ranging And Captive Pumas (Felis Concolor) And Bobcats (Lynx Rufus), Bruno B. Chomel, Yoko Kikuchi, Janice S. Martenson, Melodie E. Roelke-Parker, Chao Chin Chang, Rickie W. Kasten, Janet E. Foley, John Laudre, Kerry Murphy, Pamela K. Swift, Vicki L. Kramer, Stephen J. O'Brien

Biology Faculty Articles

Bartonella henselae is the main agent of cat scratch disease in humans and domestic cats are the main reservoir of this bacterium. We conducted a serosurvey to investigate the role of American wild felids as a potential reservoir of Bartonella species. A total of 479 samples (439 serum samples and 40 Nobuto strips) collected between 1984 and 1999 from pumas (Felis concolor) and 91 samples (58 serum samples and 33 Nobuto strips) collected from bobcats (Lynx rufus) in North America, Central America and South America were screened for B. henselae antibodies. The overall prevalence of B. henselae antibodies was respectively …

The Biological Burden Of Antibiotic Resistance In Staphylococcus Aureus, Natasha Samantha Dean

Loma Linda University Electronic Theses, Dissertations & Projects

Antibiotic resistance is a major problem. Resistance is often mediated by genes on bacterial plasmids and dissemination of resistance is commonly achieved by plasmid transfer. The mechanisms of resistance that are presently understood suggest that resistance is energetically costly. If this is generally true, resistance would reduce the fitness of cells in the absence of antibiotics. We examined the hypothesis that resistance reduces the fitness of microorganism and requires continuous selection to be maintained. To test this hypothesis, we measured the effects of plasmid-borne resistance genes on cell growth by comparing the growth rates of Staphylococcus aureus with and without …

Mer1p Is A Modular Splicing Factor Whose Function Depends On The Conserved U2 Snrnp Protein Snu17p, Marc Spingola, Javier Armisen, Manuel Ares

Biology Department Faculty Works

Mer1p activates the splicing of at least three pre‐mRNAs (AMA1, MER2, MER3) during meiosis in the yeast Saccharomyces cerevisiae. We demonstrate that enhancer recognition by Mer1p is separable from Mer1p splicing activation. The C‐terminal KH‐type RNA‐binding domain of Mer1p recognizes introns that contain the Mer1p splicing enhancer, while the N‐terminal domain interacts with the spliceosome and activates splicing. Prior studies have implicated the U1 snRNP and recognition of the 5′ splice site as key elements in Mer1p‐activated splicing. We provide new evidence that Mer1p may also function at later steps of spliceosome assembly. First, Mer1p can activate splicing of introns …

Mixture Models For Assessing Differential Expression In Complex Tissues Using Microarray Data, Debashis Ghosh

The University of Michigan Department of Biostatistics Working Paper Series

The use of DNA microarrays has become quite popular in many scientific and medical disciplines, such as in cancer research. One common goal of these studies is to determine which genes are differentially expressed between cancer and healthy tissue, or more generally, between two experimental conditions. A major complication in the molecular profiling of tumors using gene expression data is that the data represent a combination of tumor and normal cells. Much of the methodology developed for assessing differential expression with microarray data has assumed that tissue samples are homogeneous. In this article, we outline a general framework for determining …

Optimal Sample Size For Multiple Testing: The Case Of Gene Expression Microarrays, Peter Muller, Giovanni Parmigiani, Christian Robert, Judith Rousseau

Johns Hopkins University, Dept. of Biostatistics Working Papers

We consider the choice of an optimal sample size for multiple comparison problems. The motivating application is the choice of the number of microarray experiments to be carried out when learning about differential gene expression. However, the approach is valid in any application that involves multiple comparisons in a large number of hypothesis tests. We discuss two decision problems in the context of this setup: the sample size selection and the decision about the multiple comparisons. We adopt a decision theoretic approach,using loss functions that combine the competing goals of discovering as many ifferentially expressed genes as possible, while keeping …

Phylogenetic Analyses Of Texas Isolates Indicate An Evolving Subtype Of The Clade B Feline Immunodeficiency Viruses, Eric A. Weaver, Ellen W. Collisson, Margaret Slater, Guan Zhu

Nebraska Center for Virology: Faculty Publications

Rigorous phylogenetic analyses were used to compare the nucleotide sequences of feline immunodeficiency virus strains isolated from Texas and throughout the world. The envelope V3-V4 sequences and capsid gene of the Texas isolates formed a cluster between subtypes B and E. Statistical comparisons with other published sequences confirmed that the Texas group is a unique cluster, possibly a new subtype, arising from subtype B.

Feline immunodeficiency virus (FIV) was initially isolated in 1987 from a cat in California with severe immunodeficiency and has been recognized as a common worldwide feline pathogen (11, 14, 19, 20, 33). FIV-infected cats exhibit a …

Patterns Of Mtdna Diversity In Northwestern North America, Ripan S. Malhi, Katherine E. Breece, Beth A. Schultz Shook, Frederika A. Kaestle, James C. Chatters, Steven Hackenberger, David Glenn Smith

All Faculty Scholarship for the College of the Sciences

The mitochondrial DNA (mtDNA) haplogroups of 54 full-blooded modern and 64 ancient Native Americans from northwestern North America were determined. The control regions of 10 modern and 30 ancient individuals were sequenced and compared. Within the Northwest, the frequency distribution for haplogroup A is geographically structured, with haplogroup A decreasing with distance from the Pacific Coast. The haplogroup A distribution suggests that a prehistoric population intrusion from the subarctic and coastal region occurred on the Columbia Plateau in prehistoric times. Overall, the mtDNA pattern in the Northwest suggests significant amounts of gene flow among Northwest Coast, Columbia Plateau, and Great …

Phylogenetic Signal And The Utility Of 12s And 16s Mtdna In Frog Phylogeny, S. Hertwig, Rafael O. De Sá, A. Haas

Biology Faculty Publications

Genes selected for a phylogenetic study need to contain conserved information that reflects the phylogenetic history at the specific taxonomic level of interest. Mitochondrial ribosomal genes have been used for a wide range of phylogenetic questions in general and in anuran systematics in particular. We checked the plausibility of phylogenetic reconstructions in anurans that were built from commonly used 12S and 16S rRNA gene sequences. For up to 27 species arranged in taxon sets of graded inclusiveness, we inferred phylogenetic hypotheses based on different apriori decisions, i.e. choice of alignment method and alignment parameters, including/excluding variable sites, choice of reconstruction …

Calibrating Observed Differential Gene Expression For The Multiplicity Of Genes On The Array, Yingye Zheng, Margaret S. Pepe

UW Biostatistics Working Paper Series

In a gene expression array study, the expression levels of thousands of genes are monitored simultaneously across various biological conditions on a small set of subjects. One goal of such studies is to explore a large pool of genes in order to select a subset of genes that appear to be differently expressed for further investigation. Of particular interest here is how to select the top k genes once genes are ranked based on their evidence for differential expression in two tissue types. We consider statistical methods that provide a more rigorous and intuitively appealing selection process for k. We …

Bioconductor: Open Software Development For Computational Biology And Bioinformatics, Robert C. Gentleman, Vincent J. Carey, Douglas J. Bates, Benjamin M. Bolstad, Marcel Dettling, Sandrine Dudoit, Byron Ellis, Laurent Gautier, Yongchao Ge, Jeff Gentry, Kurt Hornik, Torsten Hothorn, Wolfgang Huber, Stefano Iacus, Rafael Irizarry, Friedrich Leisch, Cheng Li, Martin Maechler, Anthony J. Rossini, Guenther Sawitzki, Colin Smith, Gordon K. Smyth, Luke Tierney, Yee Hwa Yang, Jianhua Zhang

Bioconductor Project Working Papers

The Bioconductor project is an initiative for the collaborative creation of extensible software for computational biology and bioinformatics. We detail some of the design decisions, software paradigms and operational strategies that have allowed a small number of researchers to provide a wide variety of innovative, extensible, software solutions in a relatively short time. The use of an object oriented programming paradigm, the adoption and development of a software package system, designing by contract, distributed development and collaboration with other projects are elements of this project's success. Individually, each of these concepts are useful and important but when combined they have …

Minnesota Banded Darters (Etheostoma Zonale) Exhibit A High Degree Of Genetic Similarity In Mitochondrial Dna Sequences Occurrence, Jean Porterfield, Molly Fee, Jessica Theorin

Journal of the Minnesota Academy of Science

Hylogeography, or the historical interpretation of population genetic data, is a useful tool for addressing historical processes like the colonization history of organisms. North American freshwater fishes have experienced glacial ebb and flow in their relatively recent past (as little as 10,000 years before present in Minnesota), and studies of variation in intraspecific DNA sequences of these fishes can shed light on their radiations into previously glaciated areas. This study assessed intraspecific variation in two mitochondrial genes of the banded darter (Etheostoma zonale) from seven Minnesota localities. A high degree of similarity was found among all individuals in the study. …

New Alleles In Calpastatin Gene Are Associated With Meat Quality Traits In Pigs, Daniel C. Ciobanu, John W. M. Vleck, S. M. Lonergan, H. Thomsen, J. C. M. Dekkers, G. S. Plastows, M. F. Rothschild

Department of Animal Science: Faculty Publications

Suggestive QTL affecting raw firmness scores and average Instron force, tenderness, juiciness, and chewiness on cooked meat were mapped to pig chromosome 2 using a three-generation intercross between Berkshire and Yorkshire pigs. Based on its function and location, the calpastatin (CAST) gene was considered to be a good candidate for the observed effects. Several missense and silent mutations were identified in CAST and haplotypes covering most of the coding region were constructed and used for association analyses with meat quality traits. Results demonstrated that one CAST haplotype was significantly associated with lower Instron force and cooking loss and …

Smart Sequence Similarity Search (S⁴) System, Zhuo Chen

Theses Digitization Project

Sequence similarity searching is commonly used to help clarify the biochemical and physiological features of newly discovered genes or proteins. An efficient similarity search relies on the choice of tools and their associated subprograms and numerous parameter settings. To assist researchers in selecting optimal programs and parameter settings for efficient sequence similarity searches, the web-based expert system, Smart Sequence Similarity Search (S4) was developed.

Multigene Metabolic Engineering Via The Chloroplast Genome, Oscar Nemesio Ruiz

Electronic Theses and Dissertations

The vast majority of valuable agronomic traits are encoded polygenetically. Chloroplast genetic engineering offers an alternate approach to multigene engineering by allowing the insertion of entire pathways in a single transformation event, while being an environmentally friendly approach. Stable integration into the chloroplast genome and transcription of the phaA gene coding for β-ketothiolase was confirmed by Southern and northern blots. Coomassie-stained gel and western blots confirmed hyperexpression of β-ketothiolase in leaves and anthers, with high enzyme activity. The transgenic lines were normal except for the male sterile phenotype, lacking pollen. Scanning electron microscopy revealed a collapsed morphology of the pollen …

Effects Of Index Selection On The Performance And Carcass Composition Of Sheep Given Foods Of Different Protein Concentrations Ad Libitum., R. M. Lewis, G. C. Emmans, G. Simm

Department of Animal Science: Faculty Publications

Sheep of a line selected on an index to increase carcass lean content at 150 days of age (selected (S); no. = 90), and an unselected control line (control (C); no. = 90), were given ad libitum foods of three different protein concentrations (192, 141 and 120 g/kg dry matter). Growth was measured from about 21 to 114 kg live weight. The carcasses of each line were analysed for lean, fat and bone at three widely varying weights in both males and females. Level of protein did not affect the extent to tohidi S was superior to C in the …

Effects Of Two Dried Forages, And A Choice Between Them, On Intake, Growth And Carcass Composition In Lambs Of Two Breeds And Their Cross, R. M. Lewis, J. M. Macfarlane, G. C. Emmans

Department of Animal Science: Faculty Publications

The effects of for age type, breed type and sex on lamb growth and carcass composition, and their changes throughout growth, were measured. The three breed types were Scottish Blackface (no. =31), Suffolk (no. =28) and their reciprocal cross (no. =30). The lambs were given ad libitum a pelleted rye grass alone, pelleted lucerne alone or a choice of both. Each lamb was scanned using X-ray computed tomography to measure the weights of fat, lean and bone in the carcass at three proportions of mature body weight (0-30, 0·45 and 0·65). Live weights and food intake data were recorded weekly. …

Predicting Population Gene Frequency From Sample Data, R. M. Lewis, B. Grundy, L. A. Kuehn

Department of Animal Science: Faculty Publications

With an increase in the number of candidate genes for important traits in livestock, effective strategies for incorporating such genes into selection programmes are increasingly important. Those strategies in part depend on the frequency of a favoured allele in a population. Since comprehensive genotyping of a population is seldom possible, we investigate the consequences of sampling strategies on the reliability of the gene frequency estimate for a bi-allelic locus. Even within a subpopulation or line, often only a proportion of individuals will be genotype tested. However, through segregation analysis, probable genotypes can be assigned to individuals that themselves were not …

Soil Characterization Using Textural Features Extracted From Gpr Data, Lameck O. Odhiambo, Robert S. Wright, Ronald E. Yoder

Department of Animal Science: Faculty Publications

Soils can be non-intrusively mapped by observing similar patterns within ground-penetrating radar (GPR) profiles. We observed that the intricate and often indiscernible textural variability found within a complex GPR image possesses important parameters that help delineate regions of similar soil characteristics. Therefore, in this study, we examined the feasibility of using textural features extracted from GPR data to automate soil characterizations. The textural features were matched to a "fingerprint" database of previous soil classifications of GPR textural features and the corresponding ground truths of soil conditions. Four textural features (energy, contrast, entropy, and homogeneity) were selected for inputs into a …

Evaluation Of Procedures To Predict Fat-Free Lean In Swine Carcasses, Rodger K. Johnson, E. P. Johnson, R. Goodwin, J. W. Mabry, R. K. Miller, O. W. Robison, H. Sellers, M. D. Tokach

Department of Animal Science: Faculty Publications

The objectives were to develop equations for predicting fat-free lean in swine carcasses and to estimate the prediction bias that was due to genetic group, sex, and dietary lysine level. Barrows and gilts (n = 1,024) from four projects conducted by the National Pork Board were evaluated by six procedures, and their carcass fat-free lean was determined. Pigs of 16 genetic groups were fed within weight groups one of four dietary regimens that differed by 0.45% in lysine content and slaughtered at weights between 89 and 163 kg. Variables in equations included carcass weight and measures of backfat depth and …

Effects Of Food Quality On Growth And Carcass Composition In Lambs Of Two Breeds And Their Cross, R. M. Lewis, J. M. Macfarlane, G. Simm, G. C. Emmans

Department of Animal Science: Faculty Publications

The effects offood quality, breed type and sex (ram and ewe) on Iamb growth and carcass composition, and their changes throughout growth, were measured. The three breed typeswereScottish Blackface (B; no. = 24), Suffolk (S; no. = 28) and their reciprocal crosses (X; no. 33). The lambs had free access to a nutritionally non-limiting food, H, or a bulky food, L. Each lamb was scanned using X-ray computed tomography to measure the weights offat, lean and bone in the carcass at three degrees of maturity (0·30, 0·45 and 0·65) in live weight. Live weight and food intake data were recorded …

Exogenous Estrogen Boosts Circulating Estradiol Concentrations And Calcium Uptake By Duodenal Tissue In Heat-Stressed Hens, K.K. Hansen, M.M. Beck, S.E. Scheideler, Erin E. Blankenship

Department of Animal Science: Faculty Publications

In the hen, heat stress (HS) disrupts shell calcification and reproductive processes, including hormone synthesis and egg production. Two studies were conducted to investigate palliative effects of exogenous estrogen or dietary vitamin D3 on Ca homeostasis and reproductive physiology during HS. Study 1: Hy-Line W36 hens were randomly assigned to thermoneutral (TN) or HS treatments and to 1 of 7 estrogen treatments: zero (control) or one Compudose 200 implant given 1, 2, 3, 8, 9, or 10 d before onset of HS. With no implant, HS reduced plasma estradiol (E2) and total Ca absorbed (CaT) by duodenal cells (P < 0.05). In TN hens with implants, plasma E2 tripled within 24 h (P < 0.05) and remained elevated (P < 0.05) through d 9. In HS hens with implants, plasma E2 rose 6-fold (P < 0.05) to equal TN+E2 concentrations and remained elevated through d 10. In TN and HS hens with implants, the rate of Ca absorption (CaTR) and CaT increased dramatically; the responses were quadratic and essentially identical. Study 2: Hy-Line W36 hens were provided diets formulated either according to NRC requirements (NRC, 1994), or with the addition of 22,000 IU/kg vitamin D3 (+VD hens). A 24-h HS episode was imposed 2 wk after initiation of the dietary regimen. Duodenal samples were collected for Ca absorption assays after the 24-h HS episode. Both CaTR and CaT in +VD hens were approximately 3-fold higher than in hens in the NVD group (P = 0.102). The results lead to the conclusion that exogenous estrogen, high levels of dietary vitamin D, or both, before a HS episode, are efficacious in alleviating at least some of the effects of HS and should be further investigated.