Genetics and Genomics Commons^™

Gene Order Phylogeny Of The Genus Prochlorococcus, Haiwei Luo, Jian Shi, William Arndt, Jijun Tang, Robert Friedman

Faculty Publications

Background
Using gene order as a phylogenetic character has the potential to resolve previously unresolved species relationships. This character was used to resolve the evolutionary history within the genus Prochlorococcus, a group of marine cyanobacteria.

Methodology/Principal Findings
Orthologous gene sets and their genomic positions were identified from 12 species of Prochlorococcus and 1 outgroup species of Synechococcus. From this data, inversion and breakpoint distance-based phylogenetic trees were computed by GRAPPA and FastME. Statistical support of the resulting topology was obtained by application of a 50% jackknife resampling technique. The result was consistent and congruent with nucleotide sequence-based and gene-content based …

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 …

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 …

Ecological Genomics: Understanding Gene And Genome Function In The Natural Environment, M. C. Ungerer, L. C. Johnson, M. A. Herman

School of Biological Sciences: Faculty Publications

The field of ecological genomics seeks to understand the genetic mechanisms underlying responses of organisms to their natural environments. This is being achieved through the application of functional genomic approaches to identify and characterize genes with ecological and evolutionary relevance. By its very nature, ecological genomics is an interdisciplinary field. In this review, we consider the significance of this new area of study from both an ecological and genomic perspective using examples from the recent literature. We submit that by considering more fully an ecological context, researchers may gain additional insights into the underlying genetic basis of ecologically relevant phenotypic …

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 …

Comparative Chloroplast Genomics: Analyses Including New Sequences From The Angiosperms Nuphar Advena And Ranunculus Macranthus, Linda A. Raubeson, Rhiannon Peery, Timothy W. Chumley, Chris Dziubek, H. Matthew Fourcade, Jeffrey L. Boore, Robert K. Jansen

All Faculty Scholarship for the College of the Sciences

Background

The number of completely sequenced plastid genomes available is growing rapidly. This array of sequences presents new opportunities to perform comparative analyses. In comparative studies, it is often useful to compare across wide phylogenetic spans and, within angiosperms, to include representatives from basally diverging lineages such as the genomes reported here: Nuphar advena (from a basal-most lineage) and Ranunculus macranthus (a basal eudicot). We report these two new plastid genome sequences and make comparisons (within angiosperms, seed plants, or all photosynthetic lineages) to evaluate features such as the status of ycf15 and ycf68 as protein coding genes, the distribution …

The Study Of Adaptation And Speciation In The Genomic Era, Jay F. Storz, Hopi E. Hoekstra

Jay F. Storz Publications

The availability of complete genome sequences and genetic linkage maps for a growing number of mammalian species is opening up exciting new opportunities for studies of evolutionary change in natural populations. For example, multilocus mapping approaches hold the promise of identifying the specific genetic changes that underlie ecological adaptation and reproductive isolation. The fact that many of the genomic resources that have been developed for Mus and Rattus are transferable to other muroid rodents means that roughly 25% of all mammalian species can now be considered ‘‘genome-enabled’’ study organisms to varying degrees. The transferability of genomic resources between model organisms …

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 …

Shelling Out For Genomics, Timothy S. Mcclintock, Charles D. Derby

Physiology Faculty Publications

A report on the symposium 'Genomic and Proteomic Approaches to Crustacean Biology' held as part of the Society for Integrative and Comparative Biology 2006 Annual Meeting, Orlando, USA, 4-8 January 2006.

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 …

Using Genome Scans Of Dna Polymorphism To Infer Adaptive Population Divergence, Jay F. Storz

Jay F. Storz Publications

Elucidating the genetic basis of adaptive population divergence is a goal of central importance in evolutionary biology. In principle, it should be possible to identify chromosomal regions involved in adaptive divergence by screening genome-wide patterns of DNA polymorphism to detect the locus-specific signature of positive directional selection. In the case of spatially separated populations that inhabit different environments or sympatric populations that exploit different ecological niches, it is possible to identify loci that underlie divergently selected traits by comparing relative levels of differentiation among large numbers of unlinked markers. In this review I first address the question of whether diversifying …

Human Rights And Genetic Discrimination: Protecting Genomics' Promise For Public Health, Anita Silvers, Michael Ashley Stein

Faculty Publications

No abstract provided.

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 …

Comparing Clustering Algorithms For Use With Genomic And Proteomic Data, Rebecca A. Olson

Theses and Dissertations

The Human Genome Project and related projects have resulted in the development of a number of new experimental and analytic tools for use in genomic and proteomic research. In the area of toxicogenomics, researchers are concerned with how genes react to exposure to certain chemicals. The United States Air Force is interested in the effect of exposure to mission-essential chemicals. Although military personnel may come into contact with chemicals such as hydrazine, risk assessment is usually very limited. On the genomic level, risk assessment is a multi-stop and multi-disciplinary process. The process begins with an experiment that exposes cells to …

1: "To Know Ourselves", The U.S. Department Of Energy, The Human Genome Project

Genomics: Past & Future

AT THE END OF THE ROAD in Little Cottonwood Canyon, near Salt Lake City, Alta is a place of near-mythic renown among skiers. In time it may well assume similar status among molecular geneticists. In December 1984, a conference there, co-sponsored by the U.S. Department of Energy, pondered a single question: Does modern DNA research offer a way of detecting tiny genetic mutations—and, in particular, of observing any increase in the mutation rate among the survivors of the Hiroshima and Nagasaki bombings and their descendants? In short the answer was, Not yet. But in an atmosphere of rare intellectual fertility, …

2: "The Mapping Of Chromosome 16", Norman A. Doggett, Raymond L. Stallings, Carl E. Hildebrand, Robert K. Moyzis

Genomics: Past & Future

Human chromosome 16 is the main focus of the mapping efforts at Los Alamos. The large photomicrograph on these opening pages illustrates the starting point for those mapping efforts, the evaluation of our chromosome-16-specific library of cloned fragments. Among the 23 pairs of human chromosomes, one pair, chromosome 16, is identified by fluorescence in-situ hybridization. Thousands of yellow fluorescent probes derived from the clone library have hybridized to both copies of chromosome 16. The high density and uniform coverage of the fluorescent signals were a strong indication that we could use the library to construct a map of overlapping cloned …