Life Sciences Commons^™

The Functions Of Animal Micrornas., Victor Ambros

Victor R. Ambros

MicroRNAs (miRNAs) are small RNAs that regulate the expression of complementary messenger RNAs. Hundreds of miRNA genes have been found in diverse animals, and many of these are phylogenetically conserved. With miRNA roles identified in developmental timing, cell death, cell proliferation, haematopoiesis and patterning of the nervous system, evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.

Effect Of Misreported Family History On Mendelian Mutation Prediction Models, Hormuzd A. Katki

Johns Hopkins University, Dept. of Biostatistics Working Papers

People with familial history of disease often consult with genetic counselors about their chance of carrying mutations that increase disease risk. To aid them, genetic counselors use Mendelian models that predict whether the person carries deleterious mutations based on their reported family history. Such models rely on accurate reporting of each member's diagnosis and age of diagnosis, but this information may be inaccurate. Commonly encountered errors in family history can significantly distort predictions, and thus can alter the clinical management of people undergoing counseling, screening, or genetic testing. We derive general results about the distortion in the carrier probability estimate …

The Bvg Virulence Control System Regulates Biofilm Formation In Bordetella Bronchiseptica, Yasuhiko Irie, Seema Mattoo, Ming H. Yuk

Biology Faculty Publications

Bordetella species utilize the BvgAS (Bordetella virulence gene) two-component signal transduction system to sense the environment and regulate gene expression among at least three phases: a virulent Bvg⁺ phase, a nonvirulent Bvg⁻ phase, and an intermediate Bvgⁱ phase. Genes expressed in the Bvg⁺ phase encode known virulence factors, including adhesins such as filamentous hemagglutinin (FHA) and fimbriae, as well as toxins such as the bifunctional adenylate cyclase/hemolysin (ACY). Previous studies showed that in the Bvgⁱ phase, FHA and fimbriae continue to be expressed, but ACY expression is significantly downregulated. In this report, we determine …

Multiple Kh Domains Of Poly C Binding Protein Are Required For Its Trans-Activation On The Proximal Promoter Of The Mu-Opioid Receptor Gene, Adnan K. Malik

Seton Hall University Dissertations and Theses (ETDs)

The mu-opioid receptor (MOR) has been shown to mediate morphine induced analgesia, addiction, and tolerance. The expression of the major product of the MOR (MOR-1) gene has been found to be driven by two promoters, a distal promoter and a proximal promoter. The proximal promoter region has been shown in previous studies to be the major promoter for the regulation of MOR gene transcription in the adult mouse brain and embryonic development. Recent studies have shown that single-stranded DNA binding proteins (such as Poly C Binding Protein) are involved in transcriptional regulation of mouse MOR gene. Poly C binding protein …

Significance Analysis Of Time Course Microarray Experiments, John D. Storey, Wenzhong Xiao, Jeffrey T. Leek, Ronald G. Tompkins, Ron W. Davis

UW Biostatistics Working Paper Series

Characterizing the genome-wide dynamic regulation of gene expression is important and will be of much interest in the future. However, there is currently no established method for identifying differentially expressed genes in a time course study. Here we propose a significance method for analyzing time course microarray studies that can be applied to the typical types of comparisons and sampling schemes. This method is applied to two studies on humans. In one study, genes are identified that show differential expression over time in response to in vivo endotoxin administration. Using our method 7409 genes are called significant at a 1% …

Chemical Genomics In Yeast, Charles Brenner

Dartmouth Scholarship

Four recent 'chemical genomic' studies, using genome-scale collections of yeast gene deletions, have presented complementary approaches to identifying gene-drug and pathway-drug interactions.Many drugs have unknown, controversial or multiple mechanisms of action. Four recent 'chemical genomic' studies, using genome-scale collections of yeast gene deletions that were either arrayed or barcoded, have presented complementary approaches to identifying gene-drug and pathway-drug interactions.

The Caenorhabditis Elegans F-Box Protein Sel-10 Promotes Female Development And May Target Fem-1 And Fem-3 For Degradation By The Proteasome, Sibylle Jager, Hillel T. Schwartz, H. Robert Horvitz, Barbara Conradt

Dartmouth Scholarship

The Caenorhabditis elegans F-box protein SEL-10 and its human homolog have been proposed to regulate LIN-12 Notch signaling by targeting for ubiquitin-mediated proteasomal degradation LIN-12 Notch proteins and SEL-12 PS1 presenilins, the latter of which have been implicated in Alzheimer's disease. We found that sel-10 is the same gene as egl-41, which previously had been defined by gain-of-function mutations that semidominantly cause masculinization of the hermaphrodite soma. Our results demonstrate that mutations causing loss-of-function of sel-10 also have masculinizing activity, indicating that sel-10 functions to promote female development. Genetically, sel-10 acts upstream of the genes fem-1, fem-2, and fem-3 and …

Restoration Of Aspen Woodland Invaded By Western Juniper: Applications Of Partial Cutting And Prescribed Fire, Jonathon D. Bates, Richard F. Miller

Aspen Bibliography

Western juniper (Juniperus occidentalis spp. occidentalis) woodlands are rapidly replacing quaking aspen (Populus tremuloides) stands throughout the northern Great Basin. Aspen stands provide important habitat for many wildlife species and contain a high diversity of understory shrubs and herbaceous species. We studies two juniper removal treatments to restore aspen woodlands in Kiger Canyon on Steens Mountain, Oregon.

Chloroplast Dna Rearrangements In Campanulaceae: Phylogenetic Utility Of Highly Rearranged Genomes, Mary E. Cosner, Linda A. Raubeson, Robert K. Jansen

All Faculty Scholarship for the College of the Sciences

Background

The Campanulaceae (the "hare bell" or "bellflower" family) is a derived angiosperm family comprised of about 600 species treated in 35 to 55 genera. Taxonomic treatments vary widely and little phylogenetic work has been done in the family. Gene order in the chloroplast genome usually varies little among vascular plants. However, chloroplast genomes of Campanulaceae represent an exception and phylogenetic analyses solely based on chloroplast rearrangement characters support a reasonably well-resolved tree.

Results

Chloroplast DNA physical maps were constructed for eighteen representatives of the family. So many gene order changes have occurred among the genomes that characterizing individual mutational …

Agribusiness Sheep Updates - 2004 Part 2, Anyou Liu, Clinton Revell, Phil Nichols, Brad Nutt, Darryl Clements, Lucy Anderton, Stephen Gherardi, Chris Oldham, Paul Sanford, John Gladman, G. E. Donald, A. Edirisinghe, D. A. Henry, S. P. Gittins, R. C. G. Smith, Roy Butler, Kelly Pearce, David Masters, David Pethick, Andrew Thompson, Ken Hart, Johan Greeff, Beth Paganoni, Rachel Kirby, Matt Ryan, Kira Butler, Roger Heggarty, David Hopkins, Samantha Giles, Tom Plaisted, Mark Ferguson, Darren Gordon, John Young, Sandra Brown, Ian Mcfarland, John Archer, John Milton, Rob Davidson, Graeme Martin, David Lindsay, Johnathan England, Mandy Curnow, Karina P. Wood, Ashley K. White, B. Lloyd Davies, Paul M. Carberry, Mark Hyder, Mike Freer, Andrew Van Burgel, Kazue Tanaka, Andrew Peterson, Roger Wiese, Gonzalo Mata, Evan Burt, Amanda Miller, Anne Bennett, Felicity Flugge, Amir Abadi, Perry Dolling, Dean Thomas, Mike Ewing, David Lindsay, Emma Kopke, E. A. Dowling, E. K. Crossley, Brien (Ben) E. Norton, John Karlsson, Geoff Pollott, Diana Fedorenko, Darryl Clements, Robert Beard, Brown Besier, Una Ryan, Caroline Bath

Sheep Updates

Precision Pastures

Using Species Diversity to Improve Pasture Performance Anyou Liu and Clinton Revell, Department of Agriculture, Western Australia

New Annual Pasture Legumes for Sheep Graziers Phil Nichols, Angelo Loi, Brad Nutt and Darryl McClements Department of Agriculture Western Australia

Pastures from Space – Can Satellite Estimates of Pasture Growth Rate be used to Increase Farm Profit? Lucy Anderton, Stephen Gherardi and Chris Oldham Department of Agriculture Western Australia

Summer-active Perennial Grasses for Profitable Sheep Production Paul Sanford and John Gladman, Department of Agriculture, Western Australia

Pastures From Space – Validation Of Predictions Of Pasture Growth Rates DONALD, G.E^{.A …}

Agribusiness Sheep Updates - 2004 - Part 1, Mark Dolling, Len Stephens, David Thomanson, Norm Adams, Shimim Liu, Peter Buchman, Mike Paton, Dianne Evans, John Edwards, Scott Champion, Alan Langford, A. C. Schlink, J. C. Greeff, M. E. Ladyman, Kimbal M. S. Curtis, John Stanton, Stuart Adams, Neal Fogarty, Matthew Kelly, James Skerritt, Ian Mcfarland

Sheep Updates

Proceedings of the Agribusiness Sheep Updates - 2004 Forward Dr Mark Dolling Manager, Sheep Industries and Pasture, Department of Agriculture Western Australia Keynotes Australian Wool Innovation Limited DR LEN STEPHENS AUSTRALIAN WOOL INNOVATION LIMITED (AWI) Commercialisation of Sheepmeat Eating Quality Outcomes, David Thomason, General Manger Marketing Meat & livestock Australia Limited PLENARY The Fitness of the Future Merino, Norm Adams and Shimin Liu, CSIRO Livestock Industries Ovine Johne’s Disease – Managing the Disease, Managing the Issues, PETER BUCKMAN, CHIEF VETERINARY OFFICER, DEPARTMENT OF AGRICULTURE WESTERN AUSTRALIA Animal Welfare – Changes in Latitudes Changes in Attitudes, Michael Paton and Dianne Evans, …

Semiparametric Quantitative-Trait-Locus Mapping: I. On Functional Growth Curves, Ying Qing Chen, Rongling Wu

U.C. Berkeley Division of Biostatistics Working Paper Series

The genetic study of certain quantitative traits in growth curves as a function of time has recently been of major scientific interest to explore the developmental evolution processes of biological subjects. Various parametric approaches in the statistical literature have been proposed to study the quantitative-trait-loci (QTL) mapping of the growth curves as multivariate outcomes. In this article, we view the growth curves as functional quantitative traits and propose some semiparametric models to relax the strong parametric assumptions which may not be always practical in reality. Appropriate inference procedures are developed to estimate the parameters of interest which characterise the possible …

Semiparametric Quantitative-Trait-Locus Mapping: Ii. On Censored Age-At-Onset, Ying Qing Chen, Chengcheng Hu, Rongling Wu

U.C. Berkeley Division of Biostatistics Working Paper Series

In genetic studies, the variation in genotypes may not only affect different inheritance patterns in qualitative traits, but may also affect the age-at-onset as quantitative trait. In this article, we use standard cross designs, such as backcross or F2, to propose some hazard regression models, namely, the additive hazards model in quantitative trait loci mapping for age-at-onset, although the developed method can be extended to more complex designs. With additive invariance of the additive hazards models in mixture probabilities, we develop flexible semiparametric methodologies in interval regression mapping without heavy computing burden. A recently developed multiple comparison procedures is adapted …

Microsatellite Marker Development And Analysis In The Eastern Oyster (Crassostrea Virginica): Confirmation Of Null Alleles And Non-Mendelian Segregation Ratios, Kimberly S. Reece, Wl Ribeiro, Pm Gaffney, Ryan Carnegie, Standish K. Allen Jr.

VIMS Articles

Eighteen microsatellite markers were developed for the Crassostrea virginica nuclear genome, including di-, tri-, and tetranucleotide microsatellite repeat regions that included perfect, imperfect, and compound repeat sequences. A reference panel with DNA from the parents and four progeny of 10 full-sib families was used for a preliminary confirmation of polymorphism at these loci and indications of null alleles. Null alleles were discovered at three loci; in two instances, primer redesign enabled their amplification. Two to five representative alleles from each locus were sequenced to ensure that the targeted loci were amplifying. The sequence analysis revealed not only variation in the …

Genetic Analysis Of Song Dialect Populations In Puget Sound White-Crowned Sparrows, Jill Soha, Douglas Nelson, Patricia Parker

Biology Department Faculty Works

The relationship between cultural variation and biological variation among natural populations has been the subject of both theoretical and empirical study. Zonotrichia leucophrys pugetensis is one of three subspecies of white-crowned sparrow known to form geographical song dialects. We investigated whether these dialects correspond to genetic differences among Z. l. pugetensis populations. We compared allele frequencies at four microsatellite loci in males from 11 sites spanning six dialects over the subspecies' range in Oregon and Washington. Cluster analysis and genotype assignment tests indicated no tendency for sample sites within dialect areas to be genetically more similar than are sites from …

Quantification And Visualization Of Ld Patterns And Identification Of Haplotype Blocks, Yan Wang, Sandrine Dudoit

U.C. Berkeley Division of Biostatistics Working Paper Series

Classical measures of linkage disequilibrium (LD) between two loci, based only on the joint distribution of alleles at these loci, present noisy patterns. In this paper, we propose a new distance-based LD measure, R, which takes into account multilocus haplotypes around the two loci in order to exploit information from neighboring loci. The LD measure R yields a matrix of pairwise distances between markers, based on the correlation between the lengths of shared haplotypes among chromosomes around these markers. Data analysis demonstrates that visualization of LD patterns through the R matrix reveals more deterministic patterns, with much less noise, than …

Accuracy Of Msi Testing In Predicting Germline Mutations Of Msh2 And Mlh1: A Case Study In Bayesian Meta-Analysis Of Diagnostic Tests Without A Gold Standard, Sining Chen, Patrice Watson, Giovanni Parmigiani

Johns Hopkins University, Dept. of Biostatistics Working Papers

Microsatellite instability (MSI) testing is a common screening procedure used to identify families that may harbor mutations of a mismatch repair gene and therefore may be at high risk for hereditary colorectal cancer. A reliable estimate of sensitivity and specificity of MSI for detecting germline mutations of mismatch repair genes is critical in genetic counseling and colorectal cancer prevention. Several studies published results of both MSI and mutation analysis on the same subjects. In this article we perform a meta-analysis of these studies and obtain estimates that can be directly used in counseling and screening. In particular we estimate the …

Differential Expression With The Bioconductor Project, Anja Von Heydebreck, Wolfgang Huber, Robert Gentleman

Bioconductor Project Working Papers

A basic, yet challenging task in the analysis of microarray gene expression data is the identification of changes in gene expression that are associated with particular biological conditions. We discuss different approaches to this task and illustrate how they can be applied using software from the Bioconductor Project. A central problem is the high dimensionality of gene expression space, which prohibits a comprehensive statistical analysis without focusing on particular aspects of the joint distribution of the genes expression levels. Possible strategies are to do univariate gene-by-gene analysis, and to perform data-driven nonspecific filtering of genes before the actual statistical analysis. …

Natural Selection Drives Altitudinal Divergence At The Albumin Locus In Deer Mice, Peromyscus Maniculatus, Jay F. Storz, Jean M. Dubach

Jay F. Storz Publications

In populations that are distributed across steep environmental gradients, the potential for local adaptation is largely determined by the spatial scale of fitness variation relative to dispersal distance. Since altitudinal gradients are generally characterized by dramatic ecological transitions over relatively short linear distances, adaptive divergence across such gradients will typically require especially strong selection to counterbalance the homogenizing effect of gene flow. Here we report the results of a study that was designed to test for evidence of adaptive divergence across an altitudinal gradient in a natural population of deer mice, Peromyscus maniculatus. We conducted a multilocus survey of …

Nonparametric Methods For Analyzing Replication Origins In Genomewide Data, Debashis Ghosh

The University of Michigan Department of Biostatistics Working Paper Series

Due to the advent of high-throughput genomic technology, it has become possible to globally monitor cellular activities on a genomewide basis. With these new methods, scientists can begin to address important biological questions. One such question involves the identification of replication origins, which are regions in chromosomes where DNA replication is initiated. In addition, one hypothesis regarding replication origins is that their locations are non-random throughout the genome. In this article, we develop methods for identification of and cluster inference regarding replication origins involving genomewide expression data. We compare several nonparametric regression methods for the identification of replication origin locations. …

Semiparametric Methods For Identification Of Tumor Progression Genes From Microarray Data, Debashis Ghosh, Arul Chinnaiyan

The University of Michigan Department of Biostatistics Working Paper Series

The use of microarray data has become quite commonplace in medical and scientific experiments. We focus here on microarray data generated from cancer studies. It is potentially important for the discovery of biomarkers to identify genes whose expression levels correlate with tumor progression. In this article, we develop statistical procedures for the identification of such genes, which we term tumor progression genes. Two methods are considered in this paper. The first is use of a proportional odds procedure, combined with false discovery rate estimation techniques to adjust for the multiple testing problem. The second method is based on order-restricted estimation …

The False Discovery Rate: A Variable Selection Perspective, Debashis Ghosh, Wei Chen, Trivellore E. Raghuanthan

The University of Michigan Department of Biostatistics Working Paper Series

In many scientific and medical settings, large-scale experiments are generating large quantities of data that lead to inferential problems involving multiple hypotheses. This has led to recent tremendous interest in statistical methods regarding the false discovery rate (FDR). Several authors have studied the properties involving FDR in a univariate mixture model setting. In this article, we turn the problem on its side; in this manuscript, we show that FDR is a by-product of Bayesian analysis of variable selection problem for a hierarchical linear regression model. This equivalence gives many Bayesian insights as to why FDR is a natural quantity to …