Escape From Preferential Retention Following Repeated Whole Genome Duplications In Plants, James C. Schnable, Xiaowu Wang, J. Chris Pires, Michael Freeling

Department of Agronomy and Horticulture: Faculty Publications

The well supported gene dosage hypothesis predicts that genes encoding proteins engaged in dose–sensitive interactions cannot be reduced back to single copies once all interacting partners are simultaneously duplicated in a whole genome duplication. The genomes of extant flowering plants are the result of many sequential rounds of whole genome duplication, yet the fraction of genomes devoted to encoding complex molecular machines does not increase as fast as expected through multiple rounds of whole genome duplications. Using parallel interspecies genomic comparisons in the grasses and crucifers, we demonstrate that genes retained as duplicates following a whole genome duplication have only …

Assembly And Automated Annotation Of The Clostridium Scatologenes Genome, Jitesh Tiwari

Masters Theses & Specialist Projects

Clostridium scatologenes is an anaerobic bacterium that demonstrates some unusual metabolic traits such as the production of 3-methyl indole. The availability of genome level sequencing has lent itself to the exploration and elucidation of unique metabolic pathways in other organisms such as Clostridium botulinum. The Clostridium scatologenes genome, with an estimated length 4.2 million bp, was sequenced by the Applied Biosystems Solid method and the Roche 454 pyrosequencing method. The resulting DNA sequences were combined and assembled into 8267 contigs with an average length of 1250 bp with the Newbler Assembler program. Comparision of published subunits of csd gene …

Genetic Predictors Of Hyperglycemia Due To Hydrochlorothiazide Therapy, Jorge L. Del Aguila

Dissertations and Theses (Open Access)

Response to pharmacological treatment is variable among individuals. Some patients respond favorably to a drug while others develop adverse reactions. Early investigations showed evidence of variation in genes that code for drug receptors, drug transporters, and drug metabolizing enzymes; and pharmacogenetics appeared as the science that studies the relationship between drug response and genetic variation.

Thiazide diuretics are the recommended first-line monotherapy for hypertension (i.e. SBP>140 or DBP>90). Even so, diuretics are associated with adverse metabolic side effects, such as hyperglycemia, which increase the risk of developing type 2 diabetes. Published approaches testing variation in candidate genes (e.g. …

Dialogues, Dilemmas, And Disclosures: Genomic Research And Incidental Findings, Lynn W. Bush, Karen H. Rothenberg

Faculty Scholarship

No abstract provided.

Genes And Plays: Bringing Elsi Issues To Life, Karen H. Rothenberg, Lynn W. Bush

Faculty Scholarship

Ethical complexities surround the promise of genomic technology and the power of genetic information as they alter conceptions of identity and dynamics within personal and professional relationships. Creative approaches such as dramatic vignettes offer a unique analytical stage for imagining the bioethical past and future. Dramatic narratives can bring to life images of differing perspectives and values when experiencing innovations in medicine. Although the scientific landscape shifts, concerns expressed in theatre from 50 years ago parallel many contemporary ELSI (ethical, legal and social implications) issues, highlighting the ongoing struggle to appreciate the impact of emerging genetic technologies on relationships. To …

Genome-Wide Analysis Of Syntenic Gene Deletion In The Grasses, James C. Schnable, Michael Freeling, Eric Lyons

Department of Agronomy and Horticulture: Faculty Publications

The grasses, Poaceae, are one of the largest and most successful angiosperm families. Like many radiations of flowering plants, the divergence of the major grass lineages was preceded by a whole-genome duplication (WGD), although these events are not rare for flowering plants. By combining identification of syntenic gene blocks with measures of gene pair divergence and different frequencies of ancient gene loss, we have separated the two subgenomes present in modern grasses. Reciprocal loss of duplicated genes or genomic regions has been hypothesized to reproductively isolate populations and, thus, speciation. However, in contrast to previous studies in yeast and teleost …

Desert Hedgehog Is A Mammal-Specific Gene Expressed During Testicular And Ovarian Development In A Marsupial, William A. O'Hara

Master's Theses

Desert hedgehog (DHH) belongs to the hedgehog gene family that act as secreted intercellular signal transducers. DHH is an essential morphogen for normal testicular development and function in both mice and humans but is not present in the avian lineage. Like other hedgehog proteins, DHH signals through the patched (PTCH) receptors 1 and 2. Here we examine the expression and protein distribution of DHH, PTCH1 and PTCH2 in the developing testes of a marsupial mammal (the tammar wallaby) to determine whether DHH signalling is a conserved factor in gonadal development in all therian mammals.

Protein Structure Networks, Lesley H. Greene

Chemistry & Biochemistry Faculty Publications

The application of the field of network science to the scientific disciplines of structural biology and biochemistry, have yielded important new insights into the nature and determinants of protein structures, function, dynamics and the folding process. Advancements in further understanding protein relationships through network science have also reshaped the way we view the connectivity of proteins in the protein universe. The canonical hierarchical classification can now be visualized for example, as a protein fold continuum. This review will survey several key advances in the expanding area of research being conducted to study protein structures and folding using network approaches.

Efficient And Robust Rna-Seq Process For Cultured Bacteria And Complex Community Transcriptomes, Georgia Giannoukos, Dawn M. Ciulla, Katherine Huang, Brian J. Haas, Jacques Izard, Joshua Z. Levin, Jonathan Livny, Ashlee M. Earl, Dirk Gevers, Doyle V. Ward, Chad Nusbaum, Bruce W. Birren, Andreas Gnirke

Department of Food Science and Technology: Faculty Publications

We have developed a process for transcriptome analysis of bacterial communities that accommodates both intact and fragmented starting RNA and combines efficient rRNA removal with strand-specific RNA-seq. We applied this approach to an RNA mixture derived from three diverse cultured bacterial species and to RNA isolated from clinical stool samples. The resulting expression profiles were highly reproducible, enriched up to 40-fold for non-rRNA transcripts, and correlated well with profiles representing undepleted total RNA.

High-Resolution Mapping Of Open Chromatin In The Rice Genome, Wenli Zhang, Yufeng Wu, James C. Schnable, Zixian Zeng, Michael Freeling, Gregory E. Crawford, Jiming Jiang

Department of Agronomy and Horticulture: Faculty Publications

Gene expression is controlled by the complex interaction of transcription factors binding to promoters and other regulatory DNA elements. One common characteristic of the genomic regions associated with regulatory proteins is a pronounced sensitivity to DNase I digestion. We generated genome-wide high-resolution maps of DNase I hypersensitive (DH) sites from both seedling and callus tissues of rice (Oryza sativa). Approximately 25% of the DH sites from both tissues were found in putative promoters, indicating that the vast majority of the gene regulatory elements in rice are not located in promoter regions. We found 58% more DH sites in …

Genome-Wide Expression Analysis In Down Syndrome: Insight Into Immunodeficiency, Chong Li, Lei Jin, Yun Bai, Qimin Chen, Lijun Fu, Minjun Yang, Huasheng Xiao, Guoping Zhao, Shengyue Wang

PCOM Scholarly Works

Down syndrome (DS) is caused by triplication of Human chromosome 21 (Hsa21) and associated with an array of deleterious phenotypes, including mental retardation, heart defects and immunodeficiency. Genome-wide expression patterns of uncultured peripheral blood cells are useful to understanding of DS-associated immune dysfunction. We used a Human Exon microarray to characterize gene expression in uncultured peripheral blood cells derived from DS individuals and age-matched controls from two age groups: neonate (N) and child (C). A total of 174 transcript clusters (gene-level) with eight located on Hsa21 in N group and 383 transcript clusters including 56 on Hsa21 in C group …

Cryptic Distant Relatives Are Common In Both Isolated And Cosmopolitan Genetic Samples, Brenna M. Henn, Lawrence S. Hon, J. Michael Macpherson, Nicholas Eriksson, Serge Saxonov, Itsik Pe'er, Joanna Mountain

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Although a few hundred single nucleotide polymorphisms (SNPs) suffice to infer close familial relationships, high density genome-wide SNP data make possible the inference of more distant relationships such as 2nd to 9th cousinships. In order to characterize the relationship between genetic similarity and degree of kinship given a timeframe of 100–300 years, we analyzed the sharing of DNA inferred to be identical by descent (IBD) in a subset of individuals from the 23andMe customer database (n = 22,757) and from the Human Genome Diversity Panel (HGDP-CEPH, n = 952). With data from 121 populations, we show that the average amount …

High Connectivity In The Deepwater Snapper Pristipomoides Filamentosus (Lutjanidae) Across The Indo-Pacific With Isolation Of The Hawaiian Archipelago, Michelle R. Gaither, Shelley A. Jones, Christopher Kelley, Stephen J. Newman, Laurie Sorenson, Brian W. Bowen

Fisheries Research Articles

In the tropical Indo-Pacific, most phylogeographic studies have focused on the shallow-water taxa that inhabit reefs to approximately 30 m depth. Little is known about the large predatory fishes, primarily snappers (subfamily Etelinae) and groupers (subfamily Epinephelinae) that occur at 100–400 m. These long-lived, slow-growing species support fisheries across the Indo-Pacific, yet no comprehensive genetic surveys within this group have been conducted. Here we contribute the first range-wide survey of a deepwater Indo-Pacific snapper, Pristipomoides filamentosus, with special focus on Hawai'i. We applied mtDNA cytochrome b and 11 microsatellite loci to 26 samples (N = 1,222) collected across …

Comparative Genomics Of The Pathogenic Ciliate Ichthyophthirius Multifiliis, Its Free-Living Relatives And A Host Species Provide Insights Into Adoption Of A Parasitic Lifestyle And Prospects For Disease Control, Robert S. Coyne, Linda Hannick, Dhanasekaran Shanmugam, Jessica B. Hostetler, Daniel Brami, Vinita S. Joardar, Justin Johnson, Diana Radune, Irtisha Singh, Jonathan H. Badger, Ujjwal Kumar, Milton Saier, Yufeng Wang, Hong Cai, Jianying Gu, Michael W. Mather, Akhil B. Vaidya, David E. Wilkes, Vidyalakshmi Rajagopalan, David J. Asai, Chad G. Pearson, Robert C. Findly, Harry W. Dickerson, Martin Wu, Cindy Martens, Yves Van De Peer, David S. Roos, Donna M. Cassidy-Hanley, Theodore G. Clark

Publications and Research

Background

Ichthyophthirius multifiliis, commonly known as Ich, is a highly pathogenic ciliate responsible for 'white spot', a disease causing significant economic losses to the global aquaculture industry. Options for disease control are extremely limited, and Ich's obligate parasitic lifestyle makes experimental studies challenging. Unlike most well-studied protozoan parasites, Ich belongs to a phylum composed primarily of free-living members. Indeed, it is closely related to the model organism Tetrahymena thermophila. Genomic studies represent a promising strategy to reduce the impact of this disease and to understand the evolutionary transition to parasitism.

Results

We report the sequencing, assembly and annotation …

The Proteomic Response Of Ciona Intestinalis To Ocean Acidification And Acute Heat Stress: Impacts Of Global Climate Change In Coastal Marine Systems, Michael Dennis Dwyer Jr.

Biological Sciences

No abstract provided.

Large-Scale Rnai Screen Of G Protein-Coupled Receptors Involved In Larval Growth, Molting And Metamorphosis In The Red Flour Beetle, Hua Bai, Fang Zhu, Kapil Shah, Subba R. Palli

Entomology Faculty Publications

BACKGROUND: The G protein-coupled receptors (GPCRs) belong to the largest superfamily of integral cell membrane proteins and play crucial roles in physiological processes including behavior, development and reproduction. Because of their broad and diverse roles in cellular signaling, GPCRs are the therapeutic targets for many prescription drugs. However, there is no commercial pesticide targeting insect GPCRs. In this study, we employed functional genomics methods and used the red flour beetle, Tribolium castaneum, as a model system to study the physiological roles of GPCRs during the larval growth, molting and metamorphosis.

RESULTS: A total of 111 non-sensory GPCRs were identified in …

Emerging Dynamics Of Human Campylobacteriosis In Southern Ireland, Susan Bullman, Daniel Corcoran, James O'Leary, Derry O'Hare, Brigid Lucey, Roy D. Sleator

Department of Biological Sciences Publications

Infections with Campylobacter spp. pose a significant health burden worldwide. The significance of Campylobacter jejuni/Campylobacter coli infection is well appreciated but the contribution of non-C. jejuni/C. coli spp. to human gastroenteritis is largely unknown. In this study, we employed a two-tiered molecular study on 7194 patient faecal samples received by the Microbiology Department in Cork University Hospital during 2009. The first step, using EntericBio® (Serosep), a multiplex PCR system, detected Campylobacter to the genus level. The second step, utilizing Campylobacter species-specific PCR identified to the species level. A total of 340 samples were confirmed as Campylobacter genus positive, 329 of …

Phylogeography Of The Reef Fish Cephalopholis Argus(Epinephelidae) Indicates Pleistocene Isolation Across The Indo-Pacific Barrier With Contemporary Overlap In The Coral Triangle, Michelle R. Gaither, Brian W. Bowen, Tiana-Rae Bordenave, Luiz A. Rocha, Stephen J. Newman, Juan A. Gomez, Lynne Van Herwerden, Matthew T. Craig

Fisheries Research Articles

Background

The Coral Triangle (CT), bounded by the Philippines, the Malay Peninsula, and New Guinea, is the epicenter of marine biodiversity. Hypotheses that explain the source of this rich biodiversity include 1) the center of origin, 2) the center of accumulation, and 3) the region of overlap. Here we contribute to the debate with a phylogeographic survey of a widely distributed reef fish, the Peacock Grouper (Cephalopholis argus; Epinephelidae) at 21 locations (N = 550) using DNA sequence data from mtDNA cytochrome b and two nuclear introns (gonadotropin-releasing hormone and S7 ribosomal protein).

Results

Population structure was significant …

Metagenomic Biomarker Discovery And Explanation, Nicola Segata, Jacques Izard, Levi Waldron, Dirk Gevers, Larisa Miropolsky, Wendy S. Garrett, Curtis Huttenhower

Department of Food Science and Technology: Faculty Publications

This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.

Includes supplemental materials.

Screening Synteny Blocks In Pairwise Genome Comparisons Through Integer Programming, Haibao Tang, Eric Lyons, Brent S. Pedersen, James C. Schnable, Andrew H. Paterson, Michael Freeling

Department of Agronomy and Horticulture: Faculty Publications

Background:

It is difficult to accurately interpret chromosomal correspondences such as true orthology and paralogy due to significant divergence of genomes from a common ancestor. Analyses are particularly problematic among lineages that have repeatedly experienced whole genome duplication (WGD) events. To compare multiple “subgenomes” derived from genome duplications, we need to relax the traditional requirements of “one-to-one” syntenic matchings of genomic regions in order to reflect “one-to-many” or more generally “many-to-many” matchings. However this relaxation may result in the identification of synteny blocks that are derived from ancient shared WGDs that are not of interest. For many downstream analyses, we …