Genetics and Genomics Commons^™

Feature-Specific Penalized Latent Class Analysis For Genomic Data, E. Andres Houseman, Brent A. Coull, Rebecca A. Betensky

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Pseudolikelihood Approach For Simultaneous Analysis Of Array Comparative Genomic Hybridizations (Acgh), David A. Engler, Gayatry Mohapatra, David N. Louis, Rebecca Betensky

Harvard University Biostatistics Working Paper Series

DNA sequence copy number has been shown to be associated with cancer development and progression. Array-based Comparative Genomic Hybridization (aCGH) is a recent development that seeks to identify the copy number ratio at large numbers of markers across the genome. Due to experimental and biological variations across chromosomes and across hybridizations, current methods are limited to analyses of single chromosomes. We propose a more powerful approach that borrows strength across chromosomes and across hybridizations. We assume a Gaussian mixture model, with a hidden Markov dependence structure, and with random effects to allow for intertumoral variation, as well as intratumoral clonal …

Atypical Pkciota Contributes To Poor Prognosis Through Loss Of Apical-Basal Polarity And Cyclin E Overexpression In Ovarian Cancer, Astrid M. Eder, Xiaomei Sui, Daniel G. Rosen, Laura K. Nolden, Kwai Wa Cheng, John P. Lahad, Madhuri Kango-Singh, Karen H. Lu, Carla L. Warneke, Edward N. Atkinson, Isabelle Bedrosian, Khandan Keyomarsi, Wen-Lin Kuo, Joe W. Gray, Jerry C. P. Yin, Jinsong Liu, Georg Halder, Gordon B. Mills

Biology Faculty Publications

We show that atypical PKCι, which plays a critical role in the establishment and maintenance of epithelial cell polarity, is genomically amplified and overexpressed in serous epithelial ovarian cancers. Furthermore, PKCι protein is markedly increased or mislocalized in all serous ovarian cancers. An increased PKCι DNA copy number is associated with decreased progression-free survival in serous epithelial ovarian cancers. In a Drosophila in vivo epithelial tissue model, overexpression of persistently active atypical PKC results in defects in apical-basal polarity, increased Cyclin E protein expression, and increased proliferation. Similar to the Drosophila model, increased PKCι proteins levels are associated with …

Metaheuristic Applications And Their Solutions Quality, Dr. Zahid Hussain

International Conference on Information and Communication Technologies

Over the past few decades, a wide variety of classes of combinatorial problems (e.g. the assignment problem, the knapsack problem, the vehicle routing problem, etc.) have emerged - from such areas as management science, telecommunication, AI, VLSI design and many others. Many large combinatorial problems are NP-hard problems because of the combinatorial growth of their solution search space with the problem size. Such problems are commonly solved by some version of a prominent metaheuristic (e.g. Genetic Algorithms, Tabu Search, Simulated Annealing and etc.). These heuristics seek good but approximate solutions at a reasonable computational cost. These heuristics are of stochastic …

Application Of A Multiple Testing Procedure Controlling The Proportion Of False Positives To Protein And Bacterial Data, Merrill D. Birkner, Alan E. Hubbard, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Simultaneously testing multiple hypotheses is important in high-dimensional biological studies. In these situations, one is often interested in controlling the Type-I error rate, such as the proportion of false positives to total rejections (TPPFP) at a specific level, alpha. This article will present an application of the E-Bayes/Bootstrap TPPFP procedure, presented in van der Laan et al. (2005), which controls the tail probability of the proportion of false positives (TPPFP), on two biological datasets. The two data applications include firstly, the application to a mass-spectrometry dataset of two leukemia subtypes, AML and ALL. The protein data measurements include intensity and …

Digenic Control Of Colouration In The Two-Spot Gourami Trichogaster Trichopterus Trichopterus, Jack Frankel

Department of Biology Faculty Publications

Labyrinth  fishes  of  the  families  Anabantidae,  Belontiidae,Helostomatidae,  and  Osphronemidae  comprise the  tradi-tional  anabantoids,  a  group  of  about  80  relatively  small African  and  southeast  Asian  species (Linke  1991).  Many of  the  anabantoids  are  popular  with  aquarium  hobbyists because of their interesting reproductive behaviours, with males of most species brooding eggs in their mouths or in floating bubble nests (Vevers 1980; Linke 1991; Axelrod and Vorderwinkler 1995; Mills 2000). They have also beenthe focus of several environmental, morphological, and gene-tic  investigations  (Sommer  1982;  Gosline  1985;  Waki-yama  et  al. 1997;  Frankel  1992,  2001).  The  two-spot gourami,   Trichogaster  trichopterus  trichopterus  Pallas (Osphronemidae),  is  one …

Group 13 Hox Proteins Interact With The Mh2 Domain Of R-Smads And Modulate Smad Transcriptional Activation Functions Independent Of Hox Dna Binding Capability, Thomas M. Williams, Melissa E. Williams, Joanne H. Heaton, Thomas D. Gelehrter, Jeffrey W. Innis

Biology Faculty Publications

Interactions with co-factors provide a means by which HOX proteins exert specificity. To identify candidate protein interactors of HOXA13, we created and screened an E11.5–E12.5, distal limb bud yeast two-hybrid prey library. Among the interactors, we isolated the BMP-signaling effector Smad5, which interacted with the paralogous HOXD13 but not with HOXA11 or HOXA9, revealing unique interaction capabilities of the AbdB-like HOX proteins. Using deletion mutants, we determined that the MH2 domain of Smad5 is necessary for HOXA13 interaction.

This is the first report demonstrating an interaction between HOX proteins and the MH2 domain of Smad proteins. HOXA13 and HOXD13 …

Sheep Updates 2005 - Part 7, S. M. Liu, A. C. Schlink, J. R. Williams, M. E. Dowling, J. C. Greeff, Roy Butler, Keith Croker, L. G. Butler, Rob Davidson, Ken Hart, Doug Harrington, Mario D'Antuono, Julian Gardner, Geoff Duddy, R. G. Woodgate, A. Le Feuvre, A Bailey, R. B. Besier, N. Campbell, I. Carmichael, S. Love, Richard Stovold

Sheep Updates

This session covers eight papers from different authors:

POSTERS

1. Sulpher in wool and its implications for fleece weight and sheep health, SM Liu, AC Schlink, JR Williams, CSIRO Livestock Industries Wembley WA, ME Dowling,JCGreef, Department of Agriculture Western Australia.

2. Stubbles for sheep: a reality check, Roy Butler, Keith Croker, Department of Agriculture Western Australia.

3. Genetic benchmarking using artificial insemination, LC Butler, JC Greeff, Department of Agriculture Western Australia.

4. The potential lambing performances of ewes in mixed age flocks, Kieth Croker, Department of Agriculture Western Australia, Rob Davidson, WAMMCO International, formally University of Western Australia, Ken Hart, …

Sheep Updates 2005 - Part 1, R. W. Kelly, R. Kingwell, A. R. Bray, Chris Oldham, Graeme Martin, D. Blanche, D. Ferguson, Keith Crocker, Di Evans

Sheep Updates

This session covers seven papers from different authors: Boosting lambing percentages of WA sheep flocks. R.W. Kelly CSIRO Livestock Industries, Floreat WA , R. Kingwell Department of Agriculture WA,

Kiwis can fly - 30% higher lambing in 15 years, AR Bray, Meat and Wool New Zealand, Wellington, New Zealand

Rams are not a trivial expense, so what can you do to maximise on your investment? Chri Oldham, Department of Agriculture Western Australia, Graeme Martin, University of West Australia.

Care for mun - fetal programming, lamb survival and lifetime performance. RW Kelly CSIRO Livestock Industries, Floreat WA

Boost lamb survival - …

Sheep Updates 2005 - Part 4, Lucy Anderton, John Young, Rob Davidson, Keith Croker, Ken Hart, Tim Wiese, B. M. Thomson, I Williams, J. R. Briegel, J. C. Greeff, N. R. Adams, E. N. Bermingham, Sue Hatcher, Gordon Refshauge, Emma Kopke, Ross Kingwell, K. E. Kemper, M. L. Hebart, F. D. Brien, K. S. Jaensch, R. J. Grimson, D. H. Smith, Melanie Dowling, A. (Tony) Schlink, John Karlsson

Sheep Updates

This session covers twelve papers from different authors:

REPRODUCTION

1. Is it worth increasing investment to increase lambing percentages? Lucy Anderton Department of Agriculture Western Australia.

2. What value is a lamb? John Young, Farming Systems Analysis Service, Kojonup, WA

3. Providing twin-bearing ewes with extra energy at lambing produces heavier lambs at marking. Rob Davidson WAMMCO International,, formerly University of Western Australia; Keith Croker, Ken Hart, Department of Agriculture Western Australia, Tim Wiese, "Chuckem", Highbury, Western Australia.

GENETICS

4. Underlying biological cause of trade-off between meat and wool. Part 1. Wool and muscle glycogen, BM Thomson, I Williams, University …

Variation In The Fluorescence Of Green Fluorescent Protein In Various Strains Of Escherichia Coli, Paul R. Letellier Jr.

Biological Sciences Theses & Dissertations

Green fluorescent protein (GFP) was first identified in the jellyfish Aequorea victoria and generated interest due to its ability to noninvasively tag and visualize cells, cellular structures, and cellular proteins. Furthermore, the expression of green fluorescent protein in Esherichia coli cells as a tool for reporting gene expression and promotor activity has become important in the understanding of gene regulation. Expression of the gfp gene was found to vary depending on the strain of E. coli possessing the gfp gene. As a result of this fluctuation in fluorescence, gene expression and hence promotor activity may be difficult to detect or …

New Statistical Paradigms Leading To Web-Based Tools For Clinical/Translational Science, Knut M. Wittkowski

COBRA Preprint Series

As the field of functional genetics and genomics is beginning to mature, we become confronted with new challenges. The constant drop in price for sequencing and gene expression profiling as well as the increasing number of genetic and genomic variables that can be measured makes it feasible to address more complex questions. The success with rare diseases caused by single loci or genes has provided us with a proof-of-concept that new therapies can be developed based on functional genomics and genetics.

Common diseases, however, typically involve genetic epistasis, genomic pathways, and proteomic pattern. Moreover, to better understand the underlying biologi-cal …

Myod Targets Chromatin Remodeling Complexes To The Myogenin Locus Prior To Forming A Stable Dna-Bound Complex, Ivana L. De La Serna, Yasuyuki Ohkawa, Charlotte A. Berkes, Donald A. Bergstrom, Caroline S. Dacwag, Stephen J. Tapscott Fred Hutchinson Cancer Research Center, Anthony N. Imbalzano

Biology Faculty Publications

The activation of muscle-specific gene expression requires the coordinated action of muscle regulatory proteins and chromatin-remodeling enzymes. Microarray analysis performed in the presence or absence of a dominant-negative BRG1 ATPase demonstrated that approximately one-third of MyoD-induced genes were highly dependent on SWI/SNF enzymes. To understand the mechanism of activation, we performed chromatin immunoprecipitations analyzing the myogenin promoter. We found that H4 hyperacetylation preceded Brg1 binding in a MyoD-dependent manner but that MyoD binding occurred subsequent to H4 modification and Brg1 interaction. In the absence of functional SWI/SNF enzymes, muscle regulatory proteins did not bind to the myogenin promoter, thereby providing …

The Effect Of Rooibos Tea (Aspalathus Linearis) On The Survival And Transformation Of C3h-Bt1 Mouse Fibroblasts, Krista M. Beach, Paul J. Smith

Honors Capstones

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

Methods For Obtaining And Analyzing Whole Chloroplast Genome Sequences, Robert K. Jansen, Linda A. Raubeson, Jeffrey L. Boore, Claude W. Depamphilis, Timothy W. Chumley, Rosemarie C. Haberle, Stacia K. Wyman, Andrew J. Alverson, Riannon Peery, Sallie J. Herman, H. Matthew Fourcade, Jennifer V. Kuehl, Joel R. Mcneal, James Leebens-Mack, Liying Cui

All Faculty Scholarship for the College of the Sciences

During the past decade there has been a rapid increase in our understanding of plastid genome organization and evolution due to the availability of many new completely sequenced genomes. Currently there are 43 complete genomes published and ongoing projects are likely to increase this sampling to nearly 200 genomes during the next five years. Several groups of researchers including ours have been developing new techniques for gathering and analyzing entire plastid genome sequences and details of these developments are summarized in this chapter. The most important recent developments that enhance our ability to generate whole chloroplast genome sequences involve the …

Developing And Optimizing Conditions For Single Cell Genetic Analysis, Susan Adele Gitlin

Theses and Dissertations in Biomedical Sciences

Preimplantation Genetic Diagnosis (PGD) allows for couples to obtain genetic information at the embryo stage, therefore preventing lethal genetic diseases in their offspring. A recent multi-center study determined a 17% amplification failure rate overall and a 3.4% misdiagnosis rate (ESHRE PGD consortium steering committee, 2002). Experiments presented here were conducted to decrease those rates by optimizing single cell sensitivity and specificity of PGD techniques. Primer extension preamplification (PEP) was used after initial amplification failure, followed by gene specific PCR. Reamplification experiments yielded 54% amplification rates using blastomeres that previously failed amplification. In the clinical trial, four of six blastomeres were …

Searching For Differentially Expressed Gene Combinations, Marcel Dettling, Edward Gabrielson, Giovanni Parmigiani

Johns Hopkins University, Dept. of Biostatistics Working Papers

Background: Comparison of mRNA expression levels across biological samples is a widely used approach in genomics. Available data-analytic tools for deriving comprehensive lists of differentially expressed genes rely on data summaries formed using each gene in isolation from others. These approaches ignore biological relationships among genes and may miss important biological insight provided by genomics data.

Methods: We propose a fast, easily interpretable and scalable approach for identifying pairs of genes that are differentially expressed across phenotypes or experimental conditions. These are defined as pairs for which there is detectable phenotype discrimination using the joint distribution, but not from either …

Extrapair Fertilization And Genetic Similarity Of Social Mates In The Mexican Jay, John Eimes, Patricia Parker, Jerram Brown, Esther Brown

Biology Department Faculty Works

Inbreeding depression should favor the ability of females to avoid inbreeding or minimize its effects. We tested for a relationship between genetic similarity of social pairs and the occurrence of extrapair fertilization (EPF) in the Mexican jay (Aphelocoma ultramarina). Multilocus minisatellite and microsatellite DNA fingerprinting was used to detect extrapair young and measure genetic similarity between social parents. We found that 12 of 31 (39%) nests had at least one EPF and 15 of 93 (16%) young were the result of EPF. The mean DNA fingerprinting band sharing score between social mates who had at least one EPF was significantly …

From The Cover: Assignment Of An Essential Role For The Neurospora Frequency Gene In Circadian Entrainment To Temperature Cycles, Antonio M. Pregueiro, Nathan Price-Lloyd, Deborah Bell-Pedersen, Christian Heintzen, Jennifer J. Loros, Jay C. Dunlap

Dartmouth Scholarship

Circadian systems include slave oscillators and central pacemakers, and the cores of eukaryotic circadian clocks described to date are composed of transcription and translation feedback loops (TTFLs). In the model system Neurospora, normal circadian rhythmicity requires a TTFL in which a White Collar complex (WCC) activates expression of the frequency (frq) gene, and the FRQ protein feeds back to attenuate that activation. To further test the centrality of this TTFL to the circadian mechanism in Neurospora, we used low-amplitude temperature cycles to compare WT and frq-null strains under conditions in which a banding rhythm was elicited. WT cultures were entrained …

Relationship Among Genes Conferring Partial Resistance To Leaf Rust (Puccinia Triticina) In Wheat Lines Ci 13227 And L-574-1., Jeffery S. Lehman, Karin A. Hanson, Gregory Shaner

Biology and Earth Science Faculty Scholarship

This study describes the segregation of genes for resistance to the fungus Puccinia triticinain a cross between partially resistant wheat lines L-574-1 and CI 13227 with two and four genes for resistance, respectively. The objectives of this study were to use parental, F1, F2, and backcross populations to quantify maternal effects, degree of dominance, and transgressive segregation, and to determine whether CI 13227 and L-574-1 share any resistance genes for long latent period or small uredinia. In two experiments conducted in the greenhouse, the uppermost leaf of adult wheat plants was inoculated prior to heading with P. triticina. On days …

The Clustering Of Regression Models Method With Applications In Gene Expression Data, Li-Xuan Qin, Steven G. Self

UW Biostatistics Working Paper Series

Identification of differentially expressed genes and clustering of genes are two important and complementary objectives addressed with gene expression data. For the differential expression question, many "per-gene" analytic methods have been proposed. These methods can generally be characterized as using a regression function to independently model the observations for each gene; various adjustments for multiplicity are then used to interpret the statistical significance of these per-gene regression models over the collection of genes analyzed. Motivated by this common structure of per-gene models, we propose a new model-based clustering method -- the clustering of regression models method, which groups genes that …

Cluster Analysis Of Genomic Data With Applications In R, Katherine S. Pollard, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

In this paper, we provide an overview of existing partitioning and hierarchical clustering algorithms in R. We discuss statistical issues and methods in choosing the number of clusters, the choice of clustering algorithm, and the choice of dissimilarity matrix. In particular, we illustrate how the bootstrap can be employed as a statistical method in cluster analysis to establish the reproducibility of the clusters and the overall variability of the followed procedure. We also show how to visualize a clustering result by plotting ordered dissimilarity matrices in R. We present a new R package, hopach, which implements the hybrid clustering method, …

The Genetics Of Ray Pattern Variation In Caenorhabditis Briggsae, Scott Everet Baird, Cynthia R. Davidson, Justin C. Bohrer

Biological Sciences Faculty Publications

Background: How does intraspecific variation relate to macroevolutionary change in morphology? This question can be addressed in species in which derived characters are present but not fixed. In rhabditid nematodes, the arrangement of the nine bilateral pairs of peripheral sense organs (rays) in tails of males is often the most highly divergent character between species. The development of ray pattern involves inputs from hometic gene expression patterns, TGFβ signalling, Wnt signalling, and other genetic pathways. In Caenorhabditis briggsae, strain-specific variation in ray pattern has provided an entrée into the evolution of ray pattern. Some strains were fixed for a derived …

Correlational Selection Leads To Genetic Integration Of Body Size And An Attractive Plumage Trait In Dark-Eyed Juncos, Joel Mcglothlin, Patricia Parker, Val Nolan, Ellen Ketterson

Biology Department Faculty Works

When a trait's effect on fitness depends on its interaction with other traits, the resultant selection is correlational and may lead to the integration of functionally related traits. In relation to sexual selection, when an ornamental trait interacts with phenotypic quality to determine mating success, correlational sexual selection should generate genetic correlations between the ornament and quality, leading to the evolution of honest signals. Despite its potential importance in the evolution of signal honesty, correlational sexual selection has rarely been measured in natural populations. In the dark‐eyed junco (Junco hyemalis), males with experimentally elevated values of a plumage trait (whiteness …

A Defensin-Like Gene Expressed In The Black-Legged Tick, Ixodes Scapularis (Acari: Ixodidae), Wayne L. Hynes, S. M. Ceraul, S. M. Todd, K. C. Seguin, Daniel E. Sonenshine

Biological Sciences Faculty Publications

The black-legged tick Ixodes scapularis linnaeus (Acari: Ixodidae) is an important vector of microbial pathogens. Knowledge of the tick's innate immune response, particularly defensin and other antimicrobial peptides, is important for understanding how microbes survive in this tick. A defensin gene (slnA) from I. scapularis was obtained by reverse transcription-polymerase chain reaction (RT-PCR) using mRNA extracted from tissues of female ticks. RT-PCR indicated the gene was expressed in the midgut, haemocytes, and fat-body, although no evidence of a peptide was found. Sequencing a cloned cDNA fragment revealed a 225 bp open reading frame encoding a 74 amino acid pre-prodefensin, including …

Upf1p, A Highly Conserved Protein Required For Nonsense-Mediated Mrna Decay, Interacts With The Nuclear Pore Proteins Nup100p And Nup116p, Tara Nazarenus, Rebecca Cedarberg, Ryan Bell, Joseph Cheatle, Amanda Forch, Alexis Haifley, Ann Hou, Bessie Wanja Kebaara, Christina Shields, Kate Stoysich, Rachel Taylor, Audrey L. Atkin

School of Biological Sciences: Faculty Publications

Saccharomyces cerevisiae Upf1p is a 971-amino-acid protein that is required for the nonsense-mediated mRNA decay (NMD) pathway, a pathway that degrades mRNAs with premature translational termination codons. We have identified a two-hybrid interaction between Upf1p and the nuclear pore (Nup) proteins, Nup100p and Nup116p. Both nucleoporins predominantly localize to the cytoplasmic side of the nuclear pore and participate in mRNA transport. The two-hybrid interaction between Upf1p and the nuclear pore proteins, Nup100p and Nup116p, is dependent on the presence of the C-terminal 158 amino acids of Upf1p. Nup100p and Nup116p can be coimmunoprecipitated from whole-cell extracts with Upf1p, confirming in …

Is The Ability To Regenerate Damaged Skeletal Muscle Genetically Determined? : Can Allelic Variation In The Gene, Pax7, Explain Observed Differences In Recovery Of Force Following Damage By Eccentric Exercise?, Zoran Groznica

Theses : Honours

High force eccentric muscle actions, during forcibly lengthening contracting muscle, have been found to produce pronounced muscle damage, especially if exercise is unaccustomed. A cascade of events is initiated in order to repair damaged skeletal muscle tissue including degeneration and regeneration processes. For the duration of muscle regeneration, satellite cells are the primary source of new myoblasts in adult muscle. This process requires activation of quiescent mononucleated satellite cells which proliferate, differentiate and fuse together to form fully functional muscle fibres. The satellite cells are specified by the gene, Pax7, during development. Experimental studies of Pax7 null mice that lack …

Tumor Response Tcf-4/Β-Catenin Regulatory Elements For Enhancing Cancer Gene Therapies, Saurabh Kumar Gupta

Theses and Dissertations in Biomedical Sciences

Mutations in the adenomatous polyposis coli gene are frequently associated with progression of colon carcinoma and most other types of epithelial carcinomas. This usually results in stabilization of β-catenin protein levels, followed by transactivation of Tcf-4/β-catenin responsive genes. The effectiveness of a Tcf-4/β-catenin transcriptional enhancer element in combination with a c-fos or carcinoembryonic antigen promoter was tested for its ability to act as a tumor specific regulator of gene expression in a panel of human tumor and normal cell lines. Luciferase reporter assays indicated enhanced activity of the Tcf-4/β-catenin transcriptional element only in tumor cell lines, with minimal activities in …

A Bayesian Method For Finding Interactions In Genomic Studies, Wei Chen, Debashis Ghosh, Trivellore E. Raghuanthan, Sharon Kardia

The University of Michigan Department of Biostatistics Working Paper Series

An important step in building a multiple regression model is the selection of predictors. In genomic and epidemiologic studies, datasets with a small sample size and a large number of predictors are common. In such settings, most standard methods for identifying a good subset of predictors are unstable. Furthermore, there is an increasing emphasis towards identification of interactions, which has not been studied much in the statistical literature. We propose a method, called BSI (Bayesian Selection of Interactions), for selecting predictors in a regression setting when the number of predictors is considerably larger than the sample size with a focus …

Finding Cancer Subtypes In Microarray Data Using Random Projections, Debashis Ghosh

The University of Michigan Department of Biostatistics Working Paper Series

One of the benefits of profiling of cancer samples using microarrays is the generation of molecular fingerprints that will define subtypes of disease. Such subgroups have typically been found in microarray data using hierarchical clustering. A major problem in interpretation of the output is determining the number of clusters. We approach the problem of determining disease subtypes using mixture models. A novel estimation procedure of the parameters in the mixture model is developed based on a combination of random projections and the expectation-maximization algorithm. Because the approach is probabilistic, our approach provides a measure for the number of true clusters …