Genetics and Genomics Commons^™

Identification Of G1-Regulated Genes In Normally Cycling Human Cells, Maroun J. Beyrouthy, Karen E. Alexander, Amy Baldwin, Michael L. Whitfield, Hank W. Bass, Dan Mcgee, Myra M. Hurt

Dartmouth Scholarship

Background: Obtaining synchronous cell populations is essential for cell-cycle studies. Methods such as serum withdrawal or use of drugs which block cells at specific points in the cell cycle alter cellular events upon re-entry into the cell cycle. Regulatory events occurring in early G1 phase of a new cell cycle could have been overlooked. Methodology and Findings: We used a robotic mitotic shake-off apparatus to select cells in late mitosis for genome-wide gene expression studies. Two separate microarray experiments were conducted, one which involved isolation of RNA hourly for several hours from synchronous cell populations, and one experiment which examined …

Multi-Break Rearrangements And Breakpoint Re-Uses: From Circular To Linear Genomes, Max A. Alekseyev

Faculty Publications

Multi-break rearrangements break a genome into multiple fragments and further glue them together in a new order. While 2-break rearrangements represent standard reversals, fusions, fissions, and translocations, 3-break rearrangements represent a natural generalization of transpositions. Alekseyev and Pevzner (2007a, 2008a) studied multi-break rearrangements in circular genomes and further applied them to the analysis of chromosomal evolution in mammalian genomes. In this paper, we extend these results to the more difficult case of linear genomes. In particular, we give lower bounds for the rearrangement distance between linear genomes and for the breakpoint re-use rate as functions of the number and proportion …

Improving Reversal Median Computation Using Commuting Reversals And Cycle Information, William Arndt, Jijun Tang

Faculty Publications

In the past decade, genome rearrangements have attracted increasing attention from both biologists and computer scientists as a new type of data for phylogenetic analysis. Methods for reconstructing phylogeny from genome rearrangements include distance-based methods, MCMC methods, and direct optimization methods. The latter, pioneered by Sankoff and extended with the software suites GRAPPA and MGR, is the most accurate approach, but is very limited due to the difficulty of its scoring procedure—it must solve multiple instances of the reversal median problem to compute the score of a given tree. The reversal median problem is known to be NP-hard and all …

Evolution Acts On Enhancer Organization To Fine-Tune Gradient Threshold Readouts, Justin Crocker, Yoichiro Tamori, Albert Erives

Dartmouth Scholarship

The elucidation of principles governing evolution of gene regulatory sequence is critical to the study of metazoan diversification. We are therefore exploring the structure and organizational constraints of regulatory sequences by studying functionally equivalent cis-regulatory modules (CRMs) that have been evolving in parallel across several loci. Such an independent dataset allows a multi-locus study that is not hampered by nonfunctional or constrained homology. The neurogenic ectoderm enhancers (NEEs) of Drosophila melanogaster are one such class of coordinately regulated CRMs. The NEEs share a common organization of binding sites and as a set would be useful to study the relationship …

Phylogenetic Reconstruction From Transpositions, Feng Yue, Meng Zhang, Jijun Tang

Faculty Publications

Background
Because of the advent of high-throughput sequencing and the consequent reduction in the cost of sequencing, many organisms have been completely sequenced and most of their genes identified. It thus has become possible to represent whole genomes as ordered lists of gene identifiers and to study the rearrangement of these entities through computational means. As a result, genome rearrangement data has attracted increasing attentions from both biologists and computer scientists as a new type of data for phylogenetic analysis. The main events of genome rearrangements include inversions, transpositions and transversions. To date, GRAPPA and MGR are the most accurate …

Systems Approach Identifies An Organic Nitrogen-Responsive Gene Network That Is Regulated By The Master Clock Control Gene Cca1, Rodrigo A. Gutierrez, Trevor L. Stokes, Karen Thum, Xiaodong Xu, Mariana Obertello, Manpreet S. Katari, Milos Tanurdzic, Alexis Dean, Damion C. Nero, C Robertson Mcclung, Gloria M. Coruzzi

Dartmouth Scholarship

Understanding how nutrients affect gene expression will help us to understand the mechanisms controlling plant growth and development as a function of nutrient availability. Nitrate has been shown to serve as a signal for the control of gene expression in Arabidopsis. There is also evidence, on a gene-by-gene basis, that downstream products of nitrogen (N) assimilation such as glutamate (Glu) or glutamine (Gln) might serve as signals of organic N status that in turn regulate gene expression. To identify genome-wide responses to such organic N signals, Arabidopsis seedlings were transiently treated with ammonium nitrate in the presence or absence of …

Gene Rearrangement Analysis And Ancestral Order Inference From Chloroplast Genomes With Inverted Repeat, Feng Yue, Liying Cui, Claude W. Depamphilis, Bernard M.E. Moret, Jijun Tang

Faculty Publications

Background
Genome evolution is shaped not only by nucleotide substitutions, but also by structural changes including gene and genome duplications, insertions, deletions and gene order rearrangements. The most popular methods for reconstructing phylogeny from genome rearrangements include GRAPPA and MGR. However these methods are limited to cases where equal gene content or few deletions can be assumed. Since conserved duplicated regions are present in many chloroplast genomes, the inference of inverted repeats is needed in chloroplast phylogeny analysis and ancestral genome reconstruction.

Results
We extend GRAPPA and develop a new method GRAPPA-IR to handle chloroplast genomes. A test of GRAPPA-IR …

Gene Response Profiles For Daphnia Pulex Exposed To The Environmental Stressor Cadmium Reveals Novel Crustacean Metallothioneins, Joseph R. Shaw, John K. Colbourne, Jennifer C. Davey, Stephen P. Glaholt, Thomas H. Hampton, Celia Y. Chen, Carol L. Folt, Joshua W. Hamilton

Dartmouth Scholarship

Genomic research tools such as microarrays are proving to be important resources to study the complex regulation of genes that respond to environmental perturbations. A first generation cDNA microarray was developed for the environmental indicator species Daphnia pulex, to identify genes whose regulation is modulated following exposure to the metal stressor cadmium. Our experiments revealed interesting changes in gene transcription that suggest their biological roles and their potentially toxicological features in responding to this important environmental contaminant.

Genome-Wide Transcriptional Profiling Of The Cyclic Amp-Dependent Signaling Pathway During Morphogenic Transitions Of Candida Albicans, Yong-Sun Bahn, Matthew Molenda, Janet F. Staab, Courtney A. Lyman, Laura J. Gordon, Paula Sundstrom

Dartmouth Scholarship

Candida albicans is an opportunistic human fungal pathogen that causes systemic candidiasis as well as superficial mucosal candidiasis. In response to the host environment, C. albicans transitions between yeast and hyphal forms. In particular, hyphal growth is important in facilitating adhesion and invasion of host tissues, concomitant with the expression of various hypha-specific virulence factors. In previous work, we showed that the cyclic AMP (cAMP) signaling pathway plays a crucial role in morphogenic transitions and virulence of C. albicans by studying genes encoding adenylate cyclase-associated protein (CAP1) and high-affinity phosphodiesterase (PDE2) (Y. S. Bahn, J. Staab, and P. Sundstrom, Mol. …

Are There Rearrangement Hotspots In The Human Genome?, Max A. Alekseyev, Pavel A. Pevzner

Faculty Publications

In a landmark paper, Nadeau and Taylor [18] formulated the random breakage model (RBM) of chromosome evolution that postulates that there are no rearrangement hotspots in the human genome. In the next two decades, numerous studies with progressively increasing levels of resolution made RBM the de facto theory of chromosome evolution. Despite the fact that RBM had prophetic prediction power, it was recently refuted by Pevzner and Tesler [4], who introduced the fragile breakage model (FBM), postulating that the human genome is a mosaic of solid regions (with low propensity for rearrangements) and fragile regions (rearrangement hotspots). However, the rebuttal …

The Genome-Enabled Electronic Medical Record., M A Hoffman

Manuscripts, Articles, Book Chapters and Other Papers

The integration of patient-specific genomic information into the electronic medical record (EMR) will create many opportunities to improve patient care. Key to the successful incorporation of genomic information into the EMR will be the development of laboratory information systems capable of appropriately formatting molecular diagnostic and cytogenetic findings in the EMR. Due to the lack of granular genomics-related content in existing medical vocabularies, the adoption of new standards for describing clinically significant genomic information will be an important step toward recognizing the genome-enabled EMR. Appropriate capture of patient-specific genomic results in the EMR will generate new opportunities to utilize this …

Whole Genome Duplications And Contracted Breakpoint Graphs, Max A. Alekseyev, Pavel A. Pevzner

Faculty Publications

The genome halving problem, motivated by the whole genome duplication events in molecular evolution, was solved by El-Mabrouk and Sankoff in the pioneering paper [SIAM J. Comput., 32 (2003), pp. 754–792]. The El-Mabrouk–Sankoff algorithm is rather complex, inspiring a quest for a simpler solution. An alternative approach to the genome halving problem based on the notion of the contracted breakpoint graph was recently proposed in [M. A. Alekseyev and P. A. Pevzner, IEEE/ACM Trans. Comput. Biol. Bioinformatics, 4 (2007), pp. 98–107]. This new technique reveals that while the El-Mabrouk–Sankoff result is correct in most cases, it does not hold in …

Colored De Bruijn Graphs And The Genome Halving Problem, Max A. Alekseyev, Pavel A. Pevzner

Faculty Publications

Breakpoint graph analysis is a key algorithmic technique in studies of genome rearrangements. However, breakpoint graphs are defined only for genomes without duplicated genes, thus limiting their applications in rearrangement analysis. We discuss a connection between the breakpoint graphs and de Bruijn graphs that leads to a generalization of the notion of breakpoint graph for genomes with duplicated genes. We further use the generalized breakpoint graphs to study the Genome Halving Problem (first introduced and solved by Nadia El-Mabrouk and David Sankoff). The El-Mabrouk-Sankoff algorithm is rather complex, and, in this paper, we present an alternative approach that is based …

Genomeblast: A Web Tool For Small Genome Comparison, Guoqing Lu, Liying Jiang, Resa M. K. Helikar, Thaine W. Rowley, Luwen Zhang, Xianfeng Chen, Etsuko N. Moriyama

Biology Faculty Publications

Background: Comparative genomics has become an essential approach for identifying homologous gene candidates and their functions, and for studying genome evolution. There are many tools available for genome comparisons. Unfortunately, most of them are not applicable for the identification of unique genes and the inference of phylogenetic relationships in a given set of genomes.

Results: GenomeBlast is a Web tool developed for comparative analysis of multiple small genomes. A new parameter called "coverage" was introduced and used along with sequence identity to evaluate global similarity between genes. With GenomeBlast, the following results can be obtained: (1) unique genes in each …

Adaptive Evolution Of Chloroplast Genome Structure Inferred Using A Parametric Bootstrap Approach, Liying Cui, Jim Leebens-Mack, Li-San Wang, Jijun Tang, Linda Rymarquis, David B. Stern, Claude W. Depamphilis

Faculty Publications

Background
Genome rearrangements influence gene order and configuration of gene clusters in all genomes. Most land plant chloroplast DNAs (cpDNAs) share a highly conserved gene content and with notable exceptions, a largely co-linear gene order. Conserved gene orders may reflect a slow intrinsic rate of neutral chromosomal rearrangements, or selective constraint. It is unknown to what extent observed changes in gene order are random or adaptive. We investigate the influence of natural selection on gene order in association with increased rate of chromosomal rearrangement. We use a novel parametric bootstrap approach to test if directional selection is responsible for the …

Genetic And Molecular Analysis Of Phytochromes From The Filamentous Fungus Neurospora Crassa, Allan C. Froehlich, Bosl Noh, Richard D. Vierstra, Jennifer Loros, Jay C. Dunlap

Dartmouth Scholarship

Phytochromes (Phys) comprise a superfamily of red-/far-red-light-sensing proteins. Whereas higher-plant Phys that control numerous growth and developmental processes have been well described, the biochemical characteristics and functions of the microbial forms are largely unknown. Here, we describe analyses of the expression, regulation, and activities of two Phys in the filamentous fungus Neurospora crassa. In addition to containing the signature N-terminal domain predicted to covalently associate with a bilin chromophore, PHY-1 and PHY-2 contain C-terminal histidine kinase and response regulator motifs, implying that they function as hybrid two-component sensor kinases activated by light. A bacterially expressed N-terminal fragment of PHY-2 covalently …

Composite Genome Map And Recombination Parameters Derived From Three Archetypal Lineages Of Toxoplasma Gondii, Asis Khan, Sonya Taylor, Chunlei Su, Aaron J. Mackey, Jon Boyle, Robert Cole, Darius Glover, Keliang Tang, Ian T. Paulsen, Matt Berriman, John C. Boothroyd, Elmer K. Pfefferkorn, J P. Dubey, James W. Ajioka, David S. Roos, John C. Wootton, David Sibley

Dartmouth Scholarship

Toxoplasma gondii is a highly successful protozoan parasite in the phylum Apicomplexa, which contains numerous animal and human pathogens. T.gondii is amenable to cellular, biochemical, molecular and genetic studies, making it a model for the biology of this important group of parasites. To facilitate forward genetic analysis, we have developed a high-resolution genetic linkage map for T.gondii . The genetic map was used to assemble the scaffolds from a 10X shotgun whole genome sequence, thus defining 14 chromosomes with markers spaced at ∼300 kb intervals across the genome. Fourteen chromosomes were identified comprising a total genetic size of ∼592 cM …

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 …

Origins Of The Human Genome Project, Robert Mullan Cook-Deegan

RISK: Health, Safety & Environment (1990-2002)

Dr. Cook-Deegan recounts some of the scientific and political history leading to controversy about the proper mix of private and public roles in pursuing genome research and bringing its fruits to bear, e.g., in preventing and curing disease.

Book Review, Bradley J. Olson

RISK: Health, Safety & Environment (1990-2002)

Review of the following: THE CODE OF CODES: SCIENTIFIC AND SOCIAL ISSUES IN THE HUMAN GENOME PROJECT. (Daniel J. Kevles & Leroy Hood, eds., Harvard University Press 1992) [397 pp.] Contributors, figures, index, notes, preface, selected bibliography, tables. LC 91-38477, ISBN 0- 674-13645-4. [Cloth $29.95. 79 Garden Street, Cambridge MA 02138.]