Genetics and Genomics Commons^™

Assessing The Role Of Multi-Protein Complexes In Determining Phenotype, Nolwenn Le Meur, Robert Gentleman

Bioconductor Project Working Papers

Understanding regulatory mechanisms in complex biological systems is an important challenge, in particular to understand disease mechanisms, and to discover new therapies and drugs. In this paper, we consider the important question of cellular regulation of phenotype. Using single gene deletion data, we address the problem of linking a phenotype to underlying functional roles in the organism and provide a sound computational and statistical paradigm that can be extended to address more complex experimental settings such as multiple deletions. We apply the proposed approaches to publicly available data sets to demonstrate strong evidence for the involvement of multi-protein complexes in …

Design And Analysis Issues In Genome-Wide Somatic Mutation Studies Of Cancer, Giovanni Parmigiani, Simina Boca, Jimmy Lin, Kenneth W. Kinzler, Victor E. Velculescu, Bert Vogelstein

Johns Hopkins University, Dept. of Biostatistics Working Papers

The availability of the human genome sequence and progress in sequencing and bioinformatic technologies have enabled genome-wide investigation of somatic mu- tations in human cancers. This article briefly reviews challenges arising in the statistical analysis of mutational data of this kind. A first challenge is that of designing studies that efficiently allocate sequencing resources. We show that this can be addressed by two-stage designs, and demonstrate via simulations that even relatively small studies can produce lists of candidate cancer genes that are highly informative for future research efforts. A second challenge is to distinguish mutated genes that are selected for …

Differential Role Of Nadp+ And Nadph In The Activity And Structure Of Gdp-D-Mannose 4,6-Dehydratase From Two Chlorella Viruses, Floriana Fruscione, Laura Sturla, Garry Duncan, James L. Van Etten, Paola Valbuzzi, Antonio De Flora, Eleonopra Di Zanni, Michela Tonetti

James Van Etten Publications

GDP-D-mannose 4,6-dehydratase (GMD) is a key enzyme involved in the synthesis of 6-deoxyhexoses in prokaryotes and eukaryotes. Paramecium bursaria chlorella virus-1 (PBCV-1) encodes a functional GMD, which is unique among characterized GMDs because it also has a strong stereospecific NADPH-dependent reductase activity leading to GDP-D-rhamnose formation (Tonetti, M., Zanardi, D., Gurnon, J., Fruscione, F., Armirotti, A., Damonte, G., Sturla, L., De Flora, A., and Van Etten, J.L. (2003) J. Biol. Chem. 278, 21559–21565). In the present study we characterized a recombinant GMD encoded by another chlorella virus, Acanthocystis turfacea chlorella virus 1 (ATCV-1), demonstrating that it has the expected dehydratase …

2c Dna Content Values In Amaranthus (Amaranthaceae) [Abstract], Donald B. Pratt, Shalini N. Jhangiani, Robert J. Wiggers

Faculty Publications

No abstract provided.

Development And Characterization Of Microsatellite Markers For The Grain Amaranths [Abstract], Melanie A. Mallory, Rozaura V. Hall, Andrea R. Mcnabb, Donald B. Pratt, Eric N. Jellen, Peter J. Maughan

Faculty Publications

No abstract provided.

The Dynamic Evolutionary History Of The Bananaquit (Coereba Flaveola) In The Caribbean Revealed By A Multigene Analysis, Eva Bellemain, Eldredge Bermingham, Robert Ricklefs

Biology Department Faculty Works

BackgroundThe bananaquit (Coereba flaveola) is a small nectivorous and frugivorous emberizine bird (order Passeriformes) that is an abundant resident throughout the Caribbean region. We used multi-gene analyses to investigate the evolutionary history of this species throughout its distribution in the West Indies and in South and Middle America. We sequenced six mitochondrial genes (3744 base pairs) and three nuclear genes (2049 base pairs) for forty-four bananaquits and three outgroup species. We infer the ancestral area of the present-day bananaquit populations, report on the species' phylogenetic, biogeographic and evolutionary history, and propose scenarios for its diversification and range expansion.ResultsPhylogenetic concordance between …

The Search, The Jackson Laboratory

Search Magazine

No abstract provided.

Different Requirements Of The Swi/Snf Complex For Robust Nucleosome Displacement At Promoters Of Heat Shock Factor And Msn2- And Msn4-Regulated Heat Shock Genes, Tamara Y. Erkina, P. A. Tschetter, Alexander M. Erkine

Scholarship and Professional Work – COPHS

The stress response in yeast cells is regulated by at least two classes of transcription activators—HSF and Msn2/4, which differentially affect promoter chromatin remodeling. We demonstrate that the deletion of SNF2, an ATPase activity-containing subunit of the chromatin remodeling SWI/SNF complex, eliminates histone displacement, RNA polymerase II recruitment, and heat shock factor (HSF) binding at the HSP12 promoter while delaying these processes at the HSP82 and SSA4 promoters. Out of the three promoters, the double deletion of MSN2 and MSN4 eliminates both chromatin remodeling and HSF binding only at the HSP12 promoter, suggesting that Msn2/4 activators are primary determinants of …

An Improved Method For Predicting The Accuracy Of Genetic Stock Identification, Eric C. Anderson, Robin Waples, Steven T. Kalinowski

United States Department of Commerce: Staff Publications

Estimating the accuracy of genetic stock identification (GSI) that can be expected given a previously collected baseline requires simulation. The conventional method involves repeatedly simulating mixtures by resampling from the baseline, simulating new baselines by resampling from the baseline, and analyzing the simulated mixtures with the simulated baselines. We show that this overestimates the predicted accuracy of GSI. The bias is profound for closely related populations and increases as more genetic data (loci and (or) alleles) are added to the analysis. We develop a new method based on leave-one-out cross validation and show that it yields essentially unbiased estimates of …

Bmp Signaling Goes Posttranscriptional In A Microrna Sort Of Way, Catherine A. Reinke, Richard W. Carthew

Faculty Publications

Aberrant microRNA (miRNA) expression correlates with human diseases such as cardiac disorders and cancer. Treatment of such disorders using miRNA-targeted therapeutics requires a thorough understanding of miRNA regulation in vivo. A recent paper in Nature by Davis et al. expands our understanding of miRNA biogenesis and maturation, elucidating a mechanism by which extracellular signaling directs cell differentiation via posttranscriptional regulation of miRNA expression.

The Caenorhabditis Globin Gene Family Reveals Extensive Nematode-Specific Radiation And Diversification, David Hoogewijs, Sasha De Henau, Sylvia Dewilde, Luc Moens, Marjolein Couvreur, Gaetan Borgonie, Serge N. Vinogradov, Scott W. Roy, Jacques R. Vanfleteren

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Globin isoforms with variant properties and functions have been found in the pseudocoel, body wall and cuticle of various nematode species and even in the eyespots of the insect-parasite Mermis nigrescens. In fact, much higher levels of complexity exist, as shown by recent whole genome analysis studies. In silico analysis of the genome of Caenorhabditis elegans revealed an unexpectedly high number of globin genes featuring a remarkable diversity in gene structure, amino acid sequence and expression profiles.

Results

In the present study we have analyzed whole genomic data from C. briggsae, C. remanei, Pristionchus pacificus and Brugia malayi …

Rapid Bursts Of Androgen-Binding Protein (Abp) Gene Duplication Occurred Independently In Diverse Mammals, Christina M. Laukaitis, Andreas Heger, Tyler D. Blakely, Pavel Munclinger, Chris P. Ponting, Robert C. Karn

Scholarship and Professional Work - LAS

Background

The draft mouse (Mus musculus) genome sequence revealed an unexpected proliferation of gene duplicates encoding a family of secretoglobin proteins including the androgen-binding protein (ABP) α, β and γ subunits. Further investigation of 14 α-like (Abpa) and 13 β- or γ-like (Abpbg) undisrupted gene sequences revealed a rich diversity of developmental stage-, sex- and tissue-specific expression. Despite these studies, our understanding of the evolution of this gene family remains incomplete. Questions arise from imperfections in the initial mouse genome assembly and a dearth of information about the gene family structure in other rodents …

Climate Conditions In Bedded Confinement Buildings, Terry L. Mader, Leslie J. Johnson, Tami Brown-Brandl, John Gaughan

Department of Animal Science: Faculty Publications

Confinement buildings are utilized for finishing cattle to allow more efficient collection of animal waste and to buffer animals against adverse climatic conditions. Environmental data were obtained from a 29 m wide x 318 m long, solid floor, bedded confinement building with the long axis oriented east to west. The south side (front) was approximately 8.5 m high and the north (back) side is approximately 5.0 m high with 3.7 m being open (at the top). The opening was closed to within 1.0 m of the top in the winter. In general, low wind speed and/or decreased air movement associated …

Optimizing Qpcr For The Quantification Of Periodontal Pathogens In A Complex Plaque Biofilm, Sreenatha S. Kirakodu, M. Govindaswami, Michael John Novak, Jeffrey L. Ebersole, Karen F. Novak

Center for Oral Health Research Faculty Publications

Quantitative PCR (qPCR) has recently been used to quantify microorganisms in complex communities, including dental plaque biofilms. However, there is variability in the qPCR protocols being used. This study was designed to evaluate the validity of two of these variables with the intent of developing a more standardized qPCR protocol. The two variables evaluated were (1) the use of DNA content versus actual cell counts to estimate bacterial numbers in mixed plaque samples and (2) the effectiveness of three different universal primers versus species specific primers in amplifying specific target pathogens in these samples. Results lead to the development of …

A Versatile Assay For The Identification Of Rna Silencing Suppressors Based On Complementation Of Viral Movement, Jason G. Powers, Tim L. Sit, Feng Qu, T. Jack Morris, Kook-Hyung Kim, Steven A. Lommel

Nebraska Center for Virology: Faculty Publications

The cell-to-cell movement of Turnip crinkle virus (TCV) in Nicotiana benthamiana requires the presence of its coat protein (CP), a known suppressor of RNA silencing. RNA transcripts of a TCV construct containing a reporter gene (green fluorescent protein) (TCV-sGFP) in place of the CP open reading frame generated foci of three to five cells. TCV CP delivered in trans by Agrobacterium tumefaciens infiltration potentiated movement of TCV-sGFP and increased foci diameter, on average, by a factor of four. Deletion of the TCV movement proteins in TCV-sGFP (construct TCVΔ92-sGFP) abolished the movement complementation ability of TCV CP. Other known suppressors of …

Dissection Of A Qtl Hotspot On Mouse Distal Chromosome 1 That Modulates Neurobehavioral Phenotypes And Gene Expression, Khyobeni Mozhui, Daniel C. Bastiaansen, Thomas Schikorski, Xusheng Wang, Lu Lu, Robert W. Williams

Department of Animal Science: Faculty Publications

A remarkably diverse set of traits maps to a region on mouse distal chromosome 1 (Chr 1) that corresponds to human Chr 1q21–q23. This region is highly enriched in quantitative trait loci (QTLs) that control neural and behavioral phenotypes, including motor behavior, escape latency, emotionality, seizure susceptibility (Szs1), and responses to ethanol, caffeine, pentobarbital, and haloperidol. This region also controls the expression of a remarkably large number of genes, including genes that are associated with some of the classical traits that map to distal Chr 1 (e.g., seizure susceptibility). Here, we ask whether this QTL-rich region on Chr 1 …

Microarray Analysis Reveals Distinctive Signaling Between The Bed Nucleus Of The Stria Terminalis, Nucleus Accumbens, And Dorsal Striatum, Christopher M. Olsen, Yong Pandey, Shirlean Goodwin, Daniel C. Ciobanu, Lu Lu, Thomas R. Sutter, Danny G. Winder

Department of Animal Science: Faculty Publications

Microarray analysis reveals distinctive signaling between the bed nucleus of the stria terminalis, nucleus accumbens, and dorsal striatum. Physiol Genomics 32: 283–298, 2008. First published October 2, 2006; doi:10.1152/physiolgenomics.00224.2006.—To identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori …

High Rate Of Recent Transposable Element–Induced Adaptation In Drosophila Melanogaster, Josefa Gonzalez, Kapa Lenkov, Mikhail Lipatov, J. Michael Macpherson, Dmitri A. Petrov

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Although transposable elements (TEs) are known to be potent sources of mutation, their contribution to the generation of recent adaptive changes has never been systematically assessed. In this work, we conduct a genome-wide screen for adaptive TE insertions in Drosophila melanogaster that have taken place during or after the spread of this species out of Africa. We determine population frequencies of 902 of the 1,572 TEs in Release 3 of the D. melanogaster genome and identify a set of 13 putatively adaptive TEs. These 13 TEs increased in population frequency sharply after the spread out of Africa. We argue that …

Validation Case Study : Treatment Effectiveness In Aspen Vegetation Type : A Comparison Of Two Types Of Treatments On The Manti-La Sal National Forest, Diane M. Cote

Aspen Bibliography

No abstract provided.

Transcriptional Profiling Of Aphid Resistant And Susceptible Melon (Cucumis Melo) Following Cotton -Melon Aphid (Aphis Gossypii) Feeding, Preethi Samuel

Theses and Dissertations

The interaction between phloem feeding aphids Aphis gossypii (cotton-melon aphid) and Cucumis melo (melon) provides an opportunity to elucidate the means by which a host plant defends itself against aphid attack. The relationship is of scientific as well as economic importance since A. gossypii is among the most destructive insects to agriculture in the U.S. and abroad. The resistance to A. gossypii in melon is controlled at the Vat (Virus aphid transmission) locus by a major dominant gene, Vat that has the unique feature of conferring resistance to A. gossypii and resistance to transmission of non-persistent viruses by A. gossypii …

Optimal Data Partitioning And A Test Case For Ray-Finned Fishes (Actinopterygii) Based On Ten Nuclear Loci, Chenhong Li, Guoqing Lu, Guillermo Orti

Biology Faculty Publications

Data partitioning, the combined phylogenetic analysis of homogeneous blocks of data, is a common strategy used to accommodate heterogeneities in complex multilocus data sets. Variation in evolutionary rates and substitution patterns among sites are typically addressed by partitioning data by gene, codon position, or both. Excessive partitioning of the data, however, could lead to overparameterization; therefore, it seems critical to define the minimum numbers of partitions necessary to improve the overall fit of the model. We propose a new method, based on cluster analysis, to find an optimal partitioning strategy for multilocus protein-coding data sets. A heuristic exploration of alternative …

The Sacred Emergence Of Nature, Ursula Goodenough, Terrence W. Deacon

Biology Faculty Research

No abstract provided.

Droid: The Drosophila Interactions Database, A Comprehensive Resource For Annotated Gene And Protein Interactions, Jingkai Yu, Svetlana Pacifico, Guozhen Liu, Russell L. Finley Jr

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Charting the interactions among genes and among their protein products is essential for understanding biological systems. A flood of interaction data is emerging from high throughput technologies, computational approaches, and literature mining methods. Quick and efficient access to this data has become a critical issue for biologists. Several excellent multi-organism databases for gene and protein interactions are available, yet most of these have understandable difficulty maintaining comprehensive information for any one organism. No single database, for example, includes all available interactions, integrated gene expression data, and comprehensive and searchable gene information for the important model organism, Drosophila melanogaster. …

Mcm-Test: A Fuzzy-Set-Theory-Based Approach To Differential Analysis Of Gene Pathways, Lily R. Liang, Vinay Mandal, Yi Lu, Deepak Kumar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Gene pathway can be defined as a group of genes that interact with each other to perform some biological processes. Along with the efforts to identify the individual genes that play vital roles in a particular disease, there is a growing interest in identifying the roles of gene pathways in such diseases.

Results

This paper proposes an innovative fuzzy-set-theory-based approach, Multi-dimensional Cluster Misclassification test (MCM-test), to measure the significance of gene pathways in a particular disease. Experiments have been conducted on both synthetic data and real world data. Results on published diabetes gene expression dataset and a list …

Molecular Evolution Of The Cytochrome C Oxidase Subunit 5a Gene In Primates, Monica Uddin, Juan C. Opazo, Derek E. Wildman, Chet C. Sherwood, Patrick R. Hof, Morris Goodman, Lawrence I. Grossman

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Many electron transport chain (ETC) genes show accelerated rates of nonsynonymous nucleotide substitutions in anthropoid primate lineages, yet in non-anthropoid lineages the ETC proteins are typically highly conserved. Here, we test the hypothesis that COX5A, the ETC gene that encodes cytochrome c oxidase subunit 5A, shows a pattern of anthropoid-specific adaptive evolution, and investigate the distribution of this protein in catarrhine brains.

Results

In a dataset comprising 29 vertebrate taxa, including representatives from all major groups of primates, there is nearly 100% conservation of the COX5A amino acid sequence among extant, non-anthropoid placental mammals. The most recent common …

Quantitative Trait Locus Mapping For Seed Mineral Concentrations In Two Arabidopsis Thaliana Recombinant Inbred Populations, Brian M. Waters, Michael A. Grusak

Department of Agronomy and Horticulture: Faculty Publications

Biofortification of foods, achieved by increasing the concentrations of minerals such as iron (Fe) and zinc (Zn), is a goal of plant scientists. Understanding genes that influence seed mineral concentration in a model plant such as Arabidopsis could help in the development of nutritionally enhanced crop cultivars. Quantitative trait locus (QTL) mapping for seed concentrations of calcium (Ca), copper (Cu), Fe, potassium (K), magnesium (Mg), manganese (Mn), phosphorus (P), sulfur (S), and Zn was performed using two recombinant inbred line (RIL) populations, Columbia (Col) × Landsberg erecta (Ler) and Cape Verde Islands (Cvi) × Ler, grown …

Genome-Wide Identification Of Qtl For Age At Puberty In Gilts Using A Large Intercross F2 Population Between White Duroc And Erhualian, Guangcheng Yang, Jun Ren, Shijun Li, Huirong Mao, Yuanmei Guo, Zhengzhi Zou, Dongren Ren, Junwu Ma, Lusheng Huang

Psychology Faculty Publications

Puberty is a fundamental development process experienced by all reproductively competent adults, yet the specific factors regulating age at puberty remain elusive in pigs. In this study, we performed a genome scan to identify quantitative trait loci (QTL) affecting age at puberty in gilts using a White Duroc × Erhualian intercross. A total of 183 microsatellites covering 19 porcine chromosomes were genotyped in 454 F₂ gilts and their parents and grandparents in the White Duroc × Erhualian intercross. A linear regression method was used to map QTL for age at puberty via QTLexpress. One 1% genome-wise significant QTL and …

Advancing Epidemiological Science Through Computational Modeling: A Review With Novel Examples, Scott M. Duke-Sylvester, Eli N. Perencevich, Jon P. Furuno, Leslie A. Real, Holly Gaff

Biological Sciences Faculty Publications

Computational models have been successfully applied to a wide variety of research areas including infectious disease epidemiology. Especially for questions that are difficult to examine in other ways, computational models have been used to extend the range of epidemiological issues that can be addressed, advance theoretical understanding of disease processes and help identify specific intervention strategies. We explore each of these contributions to epidemiology research through discussion and examples. We also describe in detail models for raccoon rabies and methicillin-resis-tant Staphylococcus aureus, drawn from our own research, to further illustrate the role of computation in epidemiological modeling.

Ancient Dna Identification Of Early 20th Century Simian T-Cell Leukemia Virus Type 1, Sebastien Calvignac, Jean-Michel Terme, Shannon M. Hensley, Pierre Jalinot, Alex D. Greenwood, Catherine Hanni

Biological Sciences Faculty Publications

The molecular identification of proviruses from ancient tissues (and particularly from bones) remains a contentious issue. It can be expected that the copy number of proviruses will be low, which magnifies the risk of contamination with retroviruses from exogenous sources. To assess the feasibility of paleoretrovirological studies, we attempted to identify proviruses from early 20th century bones of museum specimens while following a strict ancient DNA methodology. Simian T-cell leukemia virus type 1 sequences were successfully obtained and authenticated from a Chlorocebus pygerythrus specimen. This represents the first clear evidence that it will be possible to use museum specimens to …

Genome-Wide Compensatory Changes Accompany Drug-Selected Mutations In The Plasmodium Falciparum Crt Gene, Hongying Jiang, Jigar J. Patel, Ming Yi, Jianbing Mu, Jinhui Ding, Robert Stephens, Roland A. Cooper, Michael T. Ferdig, Xin-Zhuan Su

Biological Sciences Faculty Publications

Mutations in PfCRT (Plasmodium falciparum chloroquine-resistant transporter), particularly the substitution at amino acid position 76, confer chloroquine (CQ) resistance in P. falciparum. Point mutations in the homolog of the mammalian multidrug resistance gene (pfmdr1) can also modulate the levels of CQ response. Moreover, parasites with the same pfcrt and pfmdr1 alleles exhibit a wide range of drug sensitivity, suggesting that additional genes contribute to levels of CQ resistance (CQR). Reemergence of CQ sensitive parasites after cessation of CQ use indicates that changes in PfCRT are deleterious to the parasite. Some CQR parasites, however, persist in the …