Genetics and Genomics Commons^™

In Silico Study Of Newly Synthesized Opioid Analgesics Bound To Three Opioid Receptors, Abdullah Allaoa, Mai Zahran

Publications and Research

Opioids are the most widely used drugs for the treatment of moderate to severe, chronic pain. They achieve antinociception by activation of mu (MOR-1), kappa (KOR-1), and delta (DOR-1) opioid receptors. Natural products found in kratom plant, Mitragyna speciosa, represent diverse chemical groups with opioid activity, providing opportunities to better understand opioid pharmacology. Pharmacology studies show that Mitragynine pseudoindoxyl is a mu agonist/delta antagonist opioid with a signaling bias for G-protein-mediated signaling pathways in vitro and which produced potent antinociception in vivo. Respiratory depression assays along with other behavioral testing also showed that some of the major problems …

Caenorhabditis Elegans Dbl-1/Bmp Regulates Lipid Accumulation Via Interaction With Insulin Signaling, James F. Clark, Michael Meade, Gehan Ranepura, David H. Hall, Cathy Savage-Dunn

Publications and Research

Metabolic homeostasis is coordinately controlled by diverse inputs. Understanding these regulatory networks is vital to combating metabolic disorders. The nematode Caenorhabditis elegans has emerged as a powerful, genetically tractable model system for the discovery of lipid regulatory mechanisms. Here we introduce DBL-1, the C. elegans homolog of bone morphogenetic protein 2/4 (BMP2/4), as a significant regulator of lipid homeostasis. We used neutral lipid staining and a lipid droplet marker to demonstrate that both increases and decreases in DBL-1/BMP signaling result in reduced lipid stores and lipid droplet count. We find that lipid droplet size, however, correlates positively with the level …

Cryptic Diversity And Discordance In Single‐Locus Species Delimitation Methods Within Horned Lizards (Phrynosomatidae: Phrynosoma), Christopher Blair, Robert W. Bryson Jr.

Publications and Research

Biodiversity reduction and loss continues to progress at an alarming rate, and thus there is widespread interest in utilizing rapid and efficient methods for quantifying and delimiting taxonomic diversity. Single-locus species-delimitation methods have become popular, in part due to the adoption of the DNA barcoding paradigm. These techniques can be broadly classified into tree-based and distance-based methods depending on whether species are delimited based on a constructed genealogy. Although the relative performance of these methods has been tested repeatedly with simulations, additional studies are needed to assess congruence with empirical data. We compiled a large data set of mitochondrial ND4 …

Draft Nuclear Genome Sequence Of The Halophilic And Beta-Carotene- Accumulating Green Alga Dunaliella Salina Strain Ccap19/18, Juergen Polle, Kerrie Barry, John Cushman, Jeremy Schmutz, Duc Tran, Leyla T. Hathwaik, Won C. Yin, Jerry Jenkins, Zaid Mckie-Krisberg, Simon Prochnik, Erika Lindquist, Rhyan B. Dockter, Catherine Adam, Henrik Molina, Jakob Bunkenborg, Eonseon Jin, Mark Buchheim, Jon Magnuson

Publications and Research

The halotolerant alga Dunaliella salina is a model for stress tolerance and is used commercially for production of beta-carotene (pro-vitamin A). The presented draft genome of the genuine strain CCAP19/18 will allow investigations into metabolic processes involved in regulation of stress responses, including carotenogenesis and adaptations to life in high-salinity environments.

A First Linkage Map And Downy Mildew Resistance Qtl Discovery For Sweet Basil (Ocimum Basilicum) Facilitated By Double Digestion Restriction Site Associated Dna Sequencing (Ddradseq), Robert M. Pyne, Josh Honig, Jennifer Vaiciunas, Adolfina R. Koroch, Christian Wyenandt, Stacy Bonos, James Simon

Publications and Research

Limited understanding of sweet basil (Ocimum basilicum L.) genetics and genome structure has reduced efficiency of breeding strategies. This is evidenced by the rapid, worldwide dissemination of basil downy mildew (Peronospora belbahrii) in the absence of resistant cultivars. In an effort to improve available genetic resources, expressed sequence tag simple sequence repeat (EST-SSR) and single nucleotide polymorphism (SNP) markers were developed and used to genotype the MRI x SB22 F2 mapping population, which segregates for response to downy mildew. SNP markers were generated from genomic sequences derived from double digestion restriction site associated DNA sequencing (ddRADseq). Disomic segregation was observed …

Strategies For Improving Approximate Bayesian Computation Tests For Synchronous Diversification, Isaac Overcast, Justin C. Bagley, Michael J. Hickerson

Publications and Research

Background: Estimating the variability in isolation times across co-distributed taxon pairs that may have experienced the same allopatric isolating mechanism is a core goal of comparative phylogeography. The use of hierarchical Approximate Bayesian Computation (ABC) and coalescent models to infer temporal dynamics of lineage co-diversification has been a contentious topic in recent years. Key issues that remain unresolved include the choice of an appropriate prior on the number of co-divergence events (Ψ), as well as the optimal strategies for data summarization.

Methods: Through simulation-based cross validation we explore the impact of the strategy for sorting summary statistics and the choice …

Draft Nuclear Genome, Complete Chloroplast Genome, And Complete Mitochondrial Genome For The Biofuel/ Bioproduct Feedstock Species Scenedesmus Obliquus Strain Doe0152z, S. R. Starkenburg, Juergen Polle, B. Hovde, H. E. Daligault, K. W. Davenport, A. Huang, P. Neofotis, Zaid Mckie-Krisberg

Publications and Research

The green alga Scenedesmus obliquus is an emerging platform species for the industrial production of biofuels. Here, we report the draft assembly and annotation for the nuclear, plastid, and mitochondrial genomes of S. obliquus strain DOE0152z.

Retrotransposons Are The Major Contributors To The Expansion Of The Drosophila Ananassae Muller F Element, Wilson Leung, Gerard Mcneil

Publications and Research

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (.18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors …

Large-Scale Differences In Microbial Biodiversity Discovery Between 16s Amplicon And Shotgun Sequencing, Michael Tessler, Johannes S. Neumann, Ebrahim Afshinnekoo, Michael Pineda, Rebecca Hersch, Luiz Felipe M. Velgo, Bianca T. Segovia, Fabio A. Lansac-Toha, Michael Lemke, Rob Desalle, Christopher E. Mason, Mercer R. Brugler

Publications and Research

Modern metagenomic environmental DNA studies are almost completely reliant on next-generation sequencing, making evaluations of these methods critical. We compare two next-generation sequencing techniques – amplicon and shotgun – on water samples across four of Brazil’s major river floodplain systems (Amazon, Araguaia, Paraná, and Pantanal). Less than 50% of phyla identified via amplicon sequencing were recovered from shotgun sequencing, clearly challenging the dogma that mid-depth shotgun recovers more diversity than amplicon-based approaches. Amplicon sequencing also revealed ~27% more families. Overall the amplicon data were more robust across both biodiversity and community ecology analyses at different taxonomic scales. Our work doubles …

T-Dna-Genome Junctions Form Early After Infection And Are Influenced By The Chromatin State Of The Host Genome, Shay Shilo, Pooja Tripathi, Cathy Melamed Bessudo, Oren Tzfadia, Theodore R. Muth, Avraham A. Levy

Publications and Research

Agrobacterium tumefaciens mediated T-DNA integration is a common tool for plant genome manipulation. However, there is controversy regarding whether T-DNA integration is biased towards genes or randomly distributed throughout the genome. In order to address this question, we performed high-throughput mapping of T-DNA-genome junctions obtained in the absence of selection at several time points after infection. T-DNA-genome junctions were detected as early as 6 hours post-infection. T-DNA distribution was apparently uniform throughout the chromosomes, yet local biases toward AT-rich motifs and T-DNA border sequence micro-homology were detected. Analysis of the epigenetic landscape of previously isolated sites of T-DNA integration in …

Tumor Necrosis Factor Dynamically Regulates The Mrna Stabilome In Rheumatoid Arthritis Fibroblast-Like Synoviocytes, Konstantinos Loupasakis, David Kuo, Upneet K. Sokhi, Christopher Sohn, Bethany Syracuse, Eugenia G. Giannopoulou, Sung Ho Park, Hyelim Kang, Gunnar Rätsch, Lionel B. Ivashkiv, George D. Kalliolias

Publications and Research

During rheumatoid arthritis (RA), Tumor Necrosis Factor (TNF) activates fibroblast-like synoviocytes (FLS) inducing in a temporal order a constellation of genes, which perpetuate synovial inflammation. Although the molecular mechanisms regulating TNF-induced transcription are well characterized, little is known about the impact of mRNA stability on gene expression and the impact of TNF on decay rates of mRNA transcripts in FLS. To address these issues we performed RNA sequencing and genome-wide analysis of the mRNA stabilome in RA FLS. We found that TNF induces a biphasic gene expression program: initially, the inducible transcriptome consists primarily of unstable transcripts but progressively switches …

Mutant Tdp-43 Does Not Impair Mitochondrial Bioenergetics In Vitro And In Viv, Hibiki Kawamata, Pablo Peixoto, Csaba Konrad, Gloria Palomo, Kirsten Bredvik, Meri Gerges, Federica Valsecchi, Leonard Petrucelli, John M. Ravits, Anatoly Starkov, Giovanni Manfredi

Publications and Research

Background: Mitochondrial dysfunction has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Functional studies of mitochondrial bioenergetics have focused mostly on superoxide dismutase 1 (SOD1) mutants, and showed that mutant human SOD1 impairs mitochondrial oxidative phosphorylation, calcium homeostasis, and dynamics. However, recent reports have indicated that alterations in transactivation response element DNA-binding protein 43 (TDP-43) can also lead to defects of mitochondrial morphology and dynamics. Furthermore, it was proposed that TDP-43 mutations cause oxidative phosphorylation impairment associated with respiratory chain defects and that these effects were caused by mitochondrial localization of the mutant …

From Sexless To Sexy: Why It Is Time For Human Genetics To Consider And Report Analyses Of Sex, Matthew S. Powers, Phillip H. Smith, Sherry A. Mckee, Marissa A. Ehringer

Publications and Research

Science has come a long way with regard to the consideration of sex differences in clinical and preclinical research, but one field remains behind the curve: human statistical genetics. The goal of this commentary is to raise awareness and discussion about how to best consider and evaluate possible sex effects in the context of large-scale human genetic studies. Over the course of this commentary, we reinforce the importance of interpreting genetic results in the context of biological sex, establish evidence that sex differences are not being considered in human statistical genetics, and discuss how best to conduct and report such …

Rseqrep: Rna-Seq Reports, An Open-Source Cloud-Enabled Framework For Reproducible Rna-Seq Data Processing, Analysis, And Result Reporting, Travis L. Jensen, Michael Frasketi, Kevin Conway, Leigh Villarroel, Heather Hill, Konstantinos Krampis, Johannes B. Goll

Publications and Research

RNA-Seq is increasingly being used to measure human RNA expression on a genome-wide scale. Expression profiles can be interrogated to identify and functionally characterize treatment-responsive genes. Ultimately, such controlled studies promise to reveal insights into molecular mechanisms of treatment effects, identify biomarkers, and realize personalized medicine. RNA-Seq Reports (RSEQREP) is a new open-source cloud-enabled framework that allows users to execute start-to-end gene-level RNA-Seq analysis on a preconfigured RSEQREP Amazon Virtual Machine Image (AMI) hosted by AWS or on their own Ubuntu Linux machine. The framework works with unstranded, stranded, and paired-end sequence FASTQ files stored locally, on Amazon Simple Storage …

Mirnas Associated With Prostate Cancer Risk And Progression, Hung N. Luu, Hui-Yi Lin, Karina Dalsgaard Sorensen, Olorunseun O. Ogunwobi, Nagi Kumar, Ganna Chornokur, Catherine Phelan, Dominique Jones, Lacreis Kidd, Jyotsna Batra, Kosj Yamoah, Anders Berglund, Robert J. Rounbehler, Mihi Yang, Sang Haak Lee, Nahyeon Kang, Seung Joon Kim, Jong Y. Park, Giuliano Di Pietro

Publications and Research

Prostate cancer is the most common malignancy among men in the US. Though considerable improvement in the diagnosis of prostate cancer has been achieved in the past decade, predicting disease outcome remains a major clinical challenge. Recent expression profiling studies in prostate cancer suggest microRNAs (miRNAs) may serve as potential biomarkers for prostate cancer risk and disease progression. miRNAs comprise a large family of about 22-nucleotide-long non-protein coding RNAs, regulate gene expression post-transcriptionally and participate in the regulation of numerous cellular processes. In this review, we discuss the current status of miRNA in studies evaluating the disease progression of prostate …

Differential Methylation Between Ethnic Sub-Groups Reflects The Effect Of Genetic Ancestry And Environmental Exposures, Joshua M. Galanter, Christopher R. Gignoux, Sam S. Oh, Dara Torgerson, Maria Pino-Yanes, Neeta Thakur, Celeste Eng, Donglei Hu, Scott Huntsman, Harold J. Farber, Pedro C. Avila, Emerita Brigino-Buenaventura, Michael A. Lenoir, Kelly Meade, Denise Serebrisky, William Rodriguez-Cintron, Rajesh Kumar, Jose R. Rodrıguez-Cintron, Max A. Seibold, Luisa N. Borrell, Esteban G. Burchard, Noah Zaitlen

Publications and Research

Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self- identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a …

Review Of The Algal Biology Program Within The National Alliance For Advanced Biofuels And Bioproducts, Clifford J. Unkefer, Richard T. Sayre, Jon K. Magnuson, Daniel B. Anderson, Ivan Baxter, Ian K. Balby, Judith K. Brown, Michael Carleton, Rose Ann Cattolico, Taraka Dale, Timothy P. Devarenne, C. Meghan Downes, Susan K. Dutcher, David T. Fox, Ursula Goodenough, Jan Jaworski, Jonathan E. Holladay, David M. Kramer, Andrew T. Koppisch, Mary S. Lipton, Babetta L. Marrone, Margaret Mccormick, István Molnár, John B. Mott, Kimberly L. Ogden, Ellen A. Panisko, Matteo Pellegrini, Juergen Polle, James W. Richardson, Martin Sabarsky, Shawn R. Starkenburg, Gary D. Stormo, Munehiro Teshima, Scott N. Twary, Pat J. Unkefer, Joshua S. Yuan, José A. Olivares

Publications and Research

In 2010,when the National Alliance for Advanced Biofuels and Bioproducts (NAABB) consortiumbegan, littlewas known about themolecular basis of algal biomass or oil production. Very fewalgal genome sequenceswere available and efforts to identify the best-producing wild species through bioprospecting approaches had largely stalled after the U.S. Department of Energy's Aquatic Species Program. This lack of knowledge included how reduced carbon was partitioned into storage products like triglycerides or starch and the role played bymetabolite remodeling in the accumulation of energy-dense storage products. Furthermore, genetic transformation and metabolic engineering approaches to improve algal biomass and oil yields were in their infancy. Genome …