Genetics Commons^™

Loss-Based Estimation With Cross-Validation: Applications To Microarray Data Analysis And Motif Finding, Sandrine Dudoit, Mark J. Van Der Laan, Sunduz Keles, Annette M. Molinaro, Sandra E. Sinisi, Siew Leng Teng

U.C. Berkeley Division of Biostatistics Working Paper Series

Current statistical inference problems in genomic data analysis involve parameter estimation for high-dimensional multivariate distributions, with typically unknown and intricate correlation patterns among variables. Addressing these inference questions satisfactorily requires: (i) an intensive and thorough search of the parameter space to generate good candidate estimators, (ii) an approach for selecting an optimal estimator among these candidates, and (iii) a method for reliably assessing the performance of the resulting estimator. We propose a unified loss-based methodology for estimator construction, selection, and performance assessment with cross-validation. In this approach, the parameter of interest is defined as the risk minimizer for a suitable …

Initial State Of The Drosophila Eye Before Dorsoventral Specification Is Equivalent To Ventral, Amit Singh, Kwang-Wook Choi

Biology Faculty Publications

Dorsoventral (DV) patterning is crucial for eye development in invertebrates and higher animals. DV lineage restriction is the primary event in undifferentiated early eye primordia of Drosophila. InDrosophila eye disc, a dorsal-specific GATA family transcription factor pannier (pnr) controls Iroquois-Complex (Iro-C) genes to establish the dorsal eye fate whereas Lobe (L), which is involved in controlling a Notch ligand Serrate (Ser), is specifically required for ventral growth. However, fate of eye disc cells before the onset of dorsal expression of pnr and Iro-C is not known. We show that L/Ser …

Unification Of Variance Components And Haseman-Elston Regression For Quantitative Trait Linkage Analysis, Wei-Min Chen, Karl W. Broman, Kung-Yee Liang

Johns Hopkins University, Dept. of Biostatistics Working Papers

Two of the major approaches for linkage analysis with quantitative traits in humans include variance components and Haseman-Elston regression. Previously, these have been viewed as quite separate methods. We describe a general model, fit by use of generalized estimating equations (GEE), for which the variance components and Haseman-Elston methods (including many of the extensions to the original Haseman-Elston method) are special cases, corresponding to different choices for a working covariance matrix. We also show that the regression-based test of Sham et al.(2002) is equivalent to a robust score statistic derived from our GEE approach. These results have several important implications. …

A Nested Unsupervised Approach To Identifying Novel Molecular Subtypes, Elizabeth Garrett, Giovanni Parmigiani

Johns Hopkins University, Dept. of Biostatistics Working Papers

In classification problems arising in genomics research it is common to study populations for which a broad class assignment is known (say, normal versus diseased) and one seeks to find undiscovered subclasses within one or both of the known classes. Formally, this problem can be thought of as an unsupervised analysis nested within a supervised one. Here we take the view that the nested unsupervised analysis can successfully utilize information from the entire data set for constructing and/or selecting useful predictors. Specifically, we propose a mixture model approach to the nested unsupervised problem, where the supervised information is used to …

Tree-Based Multivariate Regression And Density Estimation With Right-Censored Data , Annette M. Molinaro, Sandrine Dudoit, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We propose a unified strategy for estimator construction, selection, and performance assessment in the presence of censoring. This approach is entirely driven by the choice of a loss function for the full (uncensored) data structure and can be stated in terms of the following three main steps. (1) Define the parameter of interest as the minimizer of the expected loss, or risk, for a full data loss function chosen to represent the desired measure of performance. Map the full data loss function into an observed (censored) data loss function having the same expected value and leading to an efficient estimator …

Fisheries Research Contract Report No. 3 - Early Life History Of Abalone (Haliotis Rubra, H. Laevigata): Settlement, Survival And Early Growth. Final Report For Frdc Project 1998/306, Dr Sabine Daume

Fisheries Research Contract Reports

Australian abalone fisheries produce a high value, export-orientated products that provided 60% of the world supply in 1994 (Fleming, 2000). With wild abalone fisheries declining in countries worldwide, the interest in aquaculture products has increased substantially. The world production of abalone from aquaculture in 1999 was approximately 7,775 tonnes with only 89 tonnes (ca. 1%) being produced in Australia (Fleming, 2000). Abalone farming is expected to develop into a major industry and is a significant investment opportunity (McNamara, Victorian Aquaculture Strategy, May 1997). Future production from the numerous farms and sites either established, under construction or approved in Australia, could …

Sheep Updates 2003 - Wool, Richard Coole, Stephen Gherardi, Chris Oldham, K. Curtis, J. Stanton, Johan Greeff, Chris Oldham, Mike Hyder, Beth Pagamoni, Andrew Thompson, Tom Plaisted, Kazue Tanaka, Mike Ferguson, Darren Gordon, Andrew Peterson, Peter Sommerville

Sheep Updates

This session covers six papers from different authors:1.‘Pastures from space’ - an opportunity to increase the profitability of sheep production Richard Coole Farmer Kojonup W.A. Stephen Gherardi Chris Oldham Department of Agriculture Western Australia 2. K. Curtis Department of Agriculture WA J. Stanton Department of Agriculture WA and Curtin University 3. Is selection of ewe hogget replacement on measurement profitable? Johan Greeff Department of Agriculture of Western Australia 4. Optimising the nutrition/grazing management of ewe flocks Chris Oldham Mike Hyder Beth Paganoni Department of Agriculture of Western Australia Andrew Thompson Department of Primary Industries, Hamilton, Victoria Tom Plaisted Kazue Tanaka …

Sheep Updates 2003 - Husbandry, Paul Barrett, Kevin Bell, J Greeff, L. Butler, S. Brown, K. Hart, A. Gray, John Karlsson, Paula Coombe, Ron Mctarrart, David Scobie, Sandy White

Sheep Updates

This session covers seven papers from different authors:1. Setting up a successful, low input feedlot Paul Barrett, ‘Bimberdong’ Jerramungup 2. Effective mineral supplementation of sheep Kevin Bell, Sheep Management and Production Consultants, Kojonup, WA 3. Genetic benchmarking for WA sheep producers J. Greeff, L. Butler, S. Brown, K. Hart and A. Gray Department of Agriculture Western Australia 4. Does selecting sheep for low WEC reduce scouring? John Karlsson, Johan Greeff and Paula Coombe, Department of Agriculture Western Australia 5. Summer quarters for sheep - stubbles Ron McTaggart, Department of Agriculture Western Australia, Albany 6. Thinking about breeding Easy Care Sheep? …

Sheep Updates 2003 - Posters, Maxine Brown, Gaye Krebs, Diana Fredorenko, Kathryn Edgerton-Warburton, Evan Burt, Nazrul Islam, Roy Butler, L. G. Butler, S. R. Brown, M. F. D'Antuono, J. C. Greeff, Ken Hart, Tanya Kilminster, Rachel Kirby, M. E. Ladyman, A. C. Schlink, I. H. Williams, P. E. Vercoe, Anyou Lui, Karen Smith, Martin Bent, Matthew Young

Sheep Updates

This session covers eleven papers from different authors:1 Sheep production on annual stubbles/pastures vs lucerne Maxine Brown Gaye Krebs Muresk Institute, Curtin University Diana Fedorenko Kathryn Egerton-Warburton Centre for Cropping Systems, Department of Agriculture Western Australia 2. The value chain of the Lake Grace livestock industry Evan Burt Nazrul Islam Department of Agriculture Western Australia 3. Native pastures, Dorper sheep and the 2002 drought Roy Butler Department of Agriculture Western Australia 4. Commercial sheep breeders can improve their sheep breeding program using wether trials L.G. Butler, S.R. Brown, M.F. D’Antuono, J.C. Greeff Department of Agriculture 5. Western Australia Linked ewe …

Aphytophagy In The Miletinae (Lycaenidae): Phylogeny, Ecology, And Conservation, John Mathew

Biological Sciences Theses & Dissertations

Less than 1% of all Lepidoptera are aphytophagous; of these, a considerable proportion is found in the family Lycaenidae. The aphytophagous Lycaenidae are believed to have arisen from a mutualistic template involving ant attendance. With this association firmly in place, it is a relatively simple shift to exploitation, either of the ants themselves, through active carnivory on the brood/trophallactic feeding from adults, or by carnivory on ant-tended homopterans, with little to no interference by the ants. Among lycaenids, aphytophagy has arisen several times; most spectacularly in the subfamily Miletinae, where all of the approximately 150 species are presumed or known …

Life Cycle Of A Torrenticolous Hawaiian Chironomid (Telmatogeton Torrenticola): Stream Flow And Microhabitat Effects, M. Eric Benbow, Albert J. Burky, Carl M. Way

Biology Faculty Publications

In this study we documented the instar densities and life cycle of Telmatogeton torrenticola Terry (Chironomidae : Telmatogetoninae) from Kinihapai Stream, Maui, Hawaii. Greatest larval densities of this midge are found on substrates of high velocity, shallow flows of cascades, and splash zones of waterfalls, with lower densities in riffles. In the summer of 1994 we compared the effects of two microhabitats (termed optimal and suboptimal) on inter-instar density and relative abundance. In a second year (1995), we evaluated the effect of long-term reduced stream flow on these variables only in optimal microhabitats. A significant reduction in stream flow from …

Supervised Detection Of Regulatory Motifs In Dna Sequences, Sunduz Keles, Mark J. Van Der Laan, Sandrine Dudoit, Biao Xing, Michael B. Eisen

U.C. Berkeley Division of Biostatistics Working Paper Series

Identification of transcription factor binding sites (regulatory motifs) is a major interest in contemporary biology. We propose a new likelihood based method, COMODE, for identifying structural motifs in DNA sequences. Commonly used methods (e.g. MEME, Gibbs sampler) model binding sites as families of sequences described by a position weight matrix (PWM) and identify PWMs that maximize the likelihood of observed sequence data under a simple multinomial mixture model. This model assumes that the positions of the PWM correspond to independent multinomial distributions with four cell probabilities. We address supervising the search for DNA binding sites using the information derived from …

Phylogenetic Position Of Pterocommatinae And Cavariella, And Implications For The Origins Of Host Alternation In Aphids, Carol A. Rowe

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Aphids are morphologically simple. Their numerous hypothesized convergent reductions, such as reduced siphunculi length in association with ant attendance, have made it difficult to define morphological synapomorphies that are necessary for phylogenetic studies. Thus, I used molecular characters both to reexamine the phylogenetic relationships of Cavariella and Pterocommatinae within Aphididae, and to further map host associations and life cycles onto these phylogenies to better understand the evolutionary lability of host alternation within Aphididae. Independent and combined analyses were performed under unweighted parsimony and maximum likelihood criteria for sequences of mitochondrial cytochrome oxidase II plus tRNA-Leucine plus partial cytochrome oxidase I …

A Bt Transgene Reduces Herbivory And Enhances Fecundity In Wild Sunflowers, A. A. Snow, Diana Pilson, L. H. Rieseberg, M. J. Paulsen, N. Pleskac, M. R. Reagon, D. E. Wolf, S. M. Selbo

Diana Pilson Publications

Gene flow from transgenic crops can introduce novel traits into related species, but the ecological importance of this process is unknown. Here, we report the first empirical evidence that wild plants can benefit from a bacterial transgene under uncaged, natural conditions. Cultivated sunflower (Helianthus annuus) is known to hybridize frequently with wild sunflower (H. annuus) in the western and midwestern United States. We studied a crop-developed Bacillus thuringiensis (Bt) transgene, cry1Ac, in backcrossed wild sunflower populations. Lepidopteran damage on transgenic plants was strongly reduced relative to control plants at our two study sites, while damage …

Comparison Of Methods For Dna Isolation From Food Samples For Detection Of Shiga Toxin-Producing Escherichia Coli By Real-Time Pcr, Loree C. Heller, Carisa R. Davis, K. Kealy Peak, David Wingfield, Andrew C. Cannons, Philip T. Amuso, Jacqueline Cattani

Bioelectrics Publications

In this study, food samples were intentionally contaminated with Escherichia coli O157:H7, and then DNA was isolated by using four commercial kits. The isolated DNA samples were compared by using real-time PCR detection of the Shiga toxin genes. The four kits tested worked similarly.

Ibd Configuration Transition Matrices And Linkage Score Tests For Unilineal Relative Pairs, Sandrine Dudoit

U.C. Berkeley Division of Biostatistics Working Paper Series

Properties of transition matrices between IBD configurations are derived for four general classes of unilineal relative pairs obtained from the grand-parent/ grand-child, half-sib, avuncular, and cousin relationships. In this setting, IBD configurations are defined as orbits of groups acting on a set of inheritance vectors. Properties of the transition matrix between IBD configurations at two linked loci are derived by relating its infinitesimal generator to the adjacency matrix of a quotient graph. The second largest eigenvalue of the infinitesimal generator and its multiplicity are key in determining the form of the transition matrix and of likelihood-based linkage tests such as …

Selecting Differentially Expressed Genes From Microarray Experiments, Margaret S. Pepe, Gary M. Longton, Garnet L. Anderson, Michel Schummer

UW Biostatistics Working Paper Series

High throughput technologies, such as gene expression arrays and protein mass spectrometry, allow one to simultaneously evaluate thousands of potential biomarkers that distinguish different tissue types. Of particular interest here is cancer versus normal organ tissues. We consider statistical methods to rank genes (or proteins) in regards to differential expression between tissues. Various statistical measures are considered and we argue that two measures related to the Receiver Operating Characteristic Curve are particularly suitable for this purpose. We also propose that sampling variability in the gene rankings be quantified and suggest using the “selection probability function”, the probability distribution of rankings …

An Analysis Of Diversity In Freshwater Mussels (Bivalvia: Unionidae) Of The Cuyahoga And Rocky River Watersheds (Ohio, Usa) Based On The 16s Rrna Gene, Robert A. Krebs, Roxana N. Vlasceanu, Michael J.S. Tevesz

Biological, Geological, and Environmental Faculty Publications

The continued loss of freshwater unionid mussel species in the Great Lakes region, and particularly from Lake Erie, raises the question of how much phylogenetic and genetic variation remain in the watershed. The introduction of molecular markers into population biology offers one reproducible technique for assessing this variation. A fragment of the 16S rRNA gene of mitochondrial DNA has previously been used to infer phylogenetic relationships in the family Unionidae. Therefore, we reanalyzed these published molecular data with the addition of 12 species from the Cuyahoga and Rocky rivers in northeast Ohio. Both rivers drain to Lake Erie. The species …

Conservation And Restoration Of Pine Forest Genetic Resources In México, C. Sáenz-Romero, Amy E. Snively, R. Lindig-Cisneros

Student Published Works

Deforestation rates in México are about 670,000 ha/year. This threatens the richness of forest genetic resources in México, causing the disappearance of locally adapted populations and rare and endangered pine species. México is one of the six megadiverse countries in the world, with half of the world’s Pinus species. Pinus is one of the most economically and ecologically important forest genera in México. We suggest that delineation of seed zones and the establishment of a network of Forest Genetic Resource Conservation Units (FGRCUs), linked with forest management and ecological restoration programs will protect this valuable resource. We estimate that FGRCUs …

Dna Sequence Of Melanocortin 1-Receptor Gene In Coturnix Japonica: Correlation With Three E Locus Alleles, E, E+, Erh, Rupali B. Ugrankar

Inquiry: The University of Arkansas Undergraduate Research Journal

The melanocortin 1-receptor (MC1-R) gene plays a key role in the expression of fur and feather color in mammals and birds by regulating the distribution of two melanin pigments: eumelanin (black/brown) and pheomelanin (red/yellow). MC1-R corresponds to the classical Extension (E) locus in mice, pigs, dogs, horses, and chickens. Three E locus alleles, the wild-type (e + ), brown (E), and redhead (e rh) have been identified in Japanese quail (Coturnix japonica). To determine if the quail E locus phenotypes were due to variation in the MC1-R gene, the coding region of the MC1-R gene was PCR amplified and DNA …

Life Span Extension Of Drosophila Melanogaster: Genetic And Population Studies, Lawrence G. Harshman

Lawrence G. Harshman Publications

During the past two decades, genetic studies of model organisms have been the most important tool underlying advances in understanding the biological basis of aging and longevity. Drosophila melanogaster, the geneticist's "fruit fly," is a model organism because it has been the focus of genetic studies for more than 90 years. This review argues that studies on D. melanogaster will make an especially important contribution to the field of aging and longevity at the intersection of research on genetics, complex traits, and fly populations.

Five approaches have been used to study the genetics of longevity of D. melanogaster: …

Dna Sequence Of Melanocortin 1-Receptor Gene In Coturnix Japonica: Correlation With Three E Locus Alleles—E,E+, And Erh, Rupali Ugrankar, Kim Cheng, Ronald Okimoto

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

The melanocortin 1-receptor (MC1-R) gene plays a key role in the expression of fur and feather color in mammals and birds by regulating the distribution of two melanin pigments: eumelanin (black/brown) and pheomelanin (red/yellow). MC1-R corresponds to the classical Extension (E) locus in mice, pigs, dogs, horses, and chickens. Three E locus alleles, the wild-type (e+), brown (E), and redhead (erh) have been identified in Japanese quail (Coturnix japonica). To determine if the quail E locus phenotypes were due to variation in the MC1-R gene, the coding region of the MC1-R gene was PCR amplified and DNA sequenced using genomic …

Development Of An Automated Thiopurine Methyltransferase (Tpmt) Genotyping Assay, Mary Corcoran

Theses

Thiopurine methyltransferase (TPMT) is a cytosolic enzyme that catalyses the S- methylation of aromatic and sulphydryl compounds known as the thiopurines. These therapeutic agents are used in the treatment of acute lymphoblastic leukemia, autoimmune disorders, inflammatory bowel disease and organ transplant recipients.

Erythrocyte TPMT activity is polymorphic and patients with intermediate or deficient TPMT are at significant risk for excessive toxicity after receiving ‘standard’ doses of thiopurine medications. The activity of TPMT is inherited as an autosomal co-dominant trait. Several mutations in the TPMT gene have been described that correlate with a low activity phenotype. Three mutations G238C, G460A and …

Regression Approaches For Microarray Data Analysis, Mark R. Segal, Kam D. Dahlquist, Bruce R. Conklin

Biology Faculty Works

A variety of new procedures have been devised to handle the two sample comparison (e.g., tumor versus normal tissue) of gene expression values as measured with microarrays. Such new methods are required in part because of some defining characteristics of microarray-based studies: (i) the very large number of genes contributing expression measures which far exceeds the number of samples (observations) available, and (ii) the fact that by virtue of pathway/network relationships, the gene expression measures tend to be highly correlated. These concerns are exacerbated in the regression setting, where the objective is to relate gene expression, simultaneously for multiple genes, …

Multiple Transporters Associated With Malaria Parasite Responses To Chloroquine And Quinine, Jianbing Mu, Michael T. Ferdig, Xiaorong Feng, Deirdre A. Joy, Junhui Duan, Tetsuya Furuya, G. Subramanian, L. Aravind, Roland A. Cooper, John C. Wootton, Momia Xiong, Xin-Zhuan Su

Biological Sciences Faculty Publications

Mutations and/or overexpression of various transporters are known to confer drug resistance in a variety of organisms. In the malaria parasite Plasmodium falciparum, a homologue of P-glycoprotein, PfMDR1, has been implicated in responses to chloroquine (CO), quinine (ON) and other drugs, and a putative transporter, PfCRT, was recently demonstrated to be the key molecule in CO resistance. However, other unknown molecules are probably involved, as different parasite clones carrying the same pfcrt and pfmdr1 alleles show a wide range of quantitative responses to CO and ON. Such molecules may contribute to increasing incidences of ON treatment failure, the molecular basis …