Genetics and Genomics Commons^™

Hiding In The Lianas Of The Tree Of Life: Molecular Phylogenetics And Species Delimitation Reveal Considerable Cryptic Diversity Of New World Vine Snakes, Robert C. Jadin, Christopher Blair, Michael J. Jowers, Anthony Carmona, John C. Murphy

Publications and Research

The Brown Vine Snake, Oxybelis aeneus, is considered a single species despite the fact its distribution covers an estimated 10% of the Earth’s land surface, inhabiting a variety of ecosystems throughout North, Central, and South America and is distributed across numerous biogeographic barriers. Here we assemble a multilocus molecular dataset (i.e. cyt b, ND4, cmos, PRLR) derived from Middle American populations to examine for the first time the evolutionary history of Oxybelis and test for evidence of cryptic lineages using Bayesian and maximum likelihood criteria. Our divergence time estimates suggest that Oxybelis diverged from its sister genus, Leptophis …

Quantitative Analysis Of The Thrbcrm1-Centered Gene Regulatory Network, Benjamin Souferi, Mark M. Emerson

Publications and Research

Enhancer activity is determined by both the activity and occupancy of transcription factors as well as the specific sequences they bind. Experimental investigation of this dynamic requires the ability to manipulate components of the system, ideally in as close to an in vivo context as possible. Here we use electroporation of plasmid reporters to define critical parameters of a specific cis-regulatory element, ThrbCRM1, during retinal development. ThrbCRM1 is associated with cone photoreceptor genesis and activated in a subset of developing retinal cells that co-express the Otx2 and Onecut1 (OC1) transcription factors. Variation of reporter plasmid concentration was used to generate …

A New Insight Into Underlying Disease Mechanism Through Semi-Parametric Latent Differential Network Model, Yong He, Jiadong Ji, Lei Xie, Xinsheng Zhang, Fuzhong Xue

Publications and Research

Background

In genomic studies, to investigate how the structure of a genetic network differs between two experiment conditions is a very interesting but challenging problem, especially in high-dimensional setting. Existing literatures mostly focus on differential network modelling for continuous data. However, in real application, we may encounter discrete data or mixed data, which urges us to propose a unified differential network modelling for various data types.

Results

We propose a unified latent Gaussian copula differential network model which provides deeper understanding of the unknown mechanism than that among the observed variables. Adaptive rank-based estimation approaches are proposed with the assumption …

Gofish: A Versatile Nested Pcr Strategy For Environmental Dna Assays For Marine Vertebrates, Mark Y. Stoeckle, Mithun Das Mishu, Zachary Charlop-Powers

Publications and Research

Here we describe GoFish, a strategy for single-species environmental DNA (eDNA) presence/absence assays using nested PCR. The assays amplify a mitochondrial 12S rDNA segment with vertebrate metabarcoding primers, followed by nested PCR with M13-tailed, species-specific primers. Sanger sequencing confirms positives detected by gel electrophoresis. We first obtained 12S sequences from 77 fish specimens for 36 northwestern Atlantic taxa not well documented in GenBank. Using these and existing 12S records, we designed GoFish assays for 11 bony fish species common in the lower Hudson River estuary and tested seasonal abundance and habitat preference at two sites. Additional assays detected nine cartilaginous …

Hominoid Intraspecific Cranial Variation Mirrors Neutral Genetic Diversity, Julia M. Zichello, Karen L. Baab, Kieran P. Mcnulty, Christopher J. Raxworthy, Michael E. Steiper

Publications and Research

Natural selection, developmental constraint, and plasticity have all been invoked as explanations for intraspecific cranial variation in humans and apes. However, global patterns of human cranial variation are congruent with patterns of genetic variation, demonstrating that population history has influenced cranial variation in humans. Here we show that this finding is not unique to Homo sapiens but is also broadly evident across extant ape species. Specifically, taxa that exhibit greater intraspecific cranial shape variation also exhibit greater genetic diversity at neutral autosomal loci. Thus, cranial shape variation within hominoid taxa reflects the population history of each species. Our results suggest …

Re-Thinking Alzheimer's Disease Therapeutic Targets Using Gene-Based Tests, Man Ki Kwok, Shi Lin Lin, C Mary Schooling

Publications and Research

Background: Alzheimer's disease (AD) is a devastating condition with no known effective drug treatments. Existing drugs only alleviate symptoms. Given repeated expensive drug failures, we assessed systematically whether approved and investigational AD drugs are targeting products of genes strongly associated with AD and whether these genes are targeted by existing drugs for other indications which could be re-purposed.

Methods: We identified genes strongly associated with late-onset AD fromthe loci of genetic variants associated with AD at genome-wide-significance and from a gene-based test applied to the most extensively genotyped late-onset AD case (n=17,008)-control (n=37,154) study, the International Genomics of Alzheimer's Project. …

Able: Blockwise Site Frequency Spectrafor Inferring Complex Population Histories And Recombination, Champak R. Beeravolu, Michael J. Hickerson, Laurent A. F. Frantz, Konrad Lohse

Publications and Research

We introduce ABLE (Approximate Blockwise Likelihood Estimation), a novel simulation-based composite likelihood method that uses the blockwise site frequency spectrum to jointly infer past demography and recombination. ABLE is explicitly designed for a wide variety of data from unphased diploid genomes to genome-wide multi-locus data (for example, RADSeq) and can also accommodate arbitrarily large samples. We use simulations to demonstrate the accuracy of this method to infer complex histories of divergence and gene flow and reanalyze whole genome data from two species of orangutan. ABLE is available for download at https://github.com/champost/ABLE.

Dobi Studies, Teaches The Marvels Of Genetics, Aldemaro Romero Jr.

Publications and Research

“When I was in third grade, a parent of one of the other students brought a number of cats to the library on a Saturday and talked about how there are all these different hereditary patterns that contribute to their coat colors and appearance, like spots, stripes, and white paws. I was just hooked because I loved cats, and I said this is what I want to do.”

That’s how Dr. Krista Dobi explains why she became a geneticist. A native of North Brunswick, New Jersey, Dobi received a bachelor of arts from Princeton University and a doctorate in genetics …

Genetic Determinants Of Telomere Length In African American Youth, Andrew M. Zeiger, Marquitta J. White, Celeste Eng, Sam S. Oh, Jonathan Witonsky, Pagé C. Goddard, Maria G. Contreras, Jennifer R. Elhawary, Donglei Hu, Angel C. Y. Mak, Eunice Y. Lee, Kevin L. Keys, Lesly-Anne Samedy, Oona Risse Adams, Joaquín Magaña, Scott Huntsman, Sandra Salazar, Adam Davis, Kelley Meade, Emerita Brigino-Buenaventura, Michael A. Lenoir, Harold J. Farber, Kirsten Bibbins-Domingo, Luisa N. Borrell, Esteban G. Burchard

Publications and Research

Telomere length (TL) is associated with numerous disease states and is affected by genetic and environmental factors. However, TL has been mostly studied in adult populations of European or Asian ancestry. These studies have identified 34 TL-associated genetic variants recently used as genetic proxies for TL. The generalizability of these associations to pediatric populations and racially diverse populations, specifically of African ancestry, remains unclear. Furthermore, six novel variants associated with TL in a population of European children have been identified but not validated. We measured TL from whole blood samples of 492 healthy African American youth (children and adolescents between …

The Transcriptome Of The Bermuda Fireworm Odontosyllis Enopla (Annelida: Syllidae): A Unique Luciferase Gene Family And Putative Epitoky-Related Genes, Mercer R. Brugler, M. Teresa Aguado, Michael Tessler, Mark Siddall

Publications and Research

The Bermuda fireworm Odontosyllis enopla exhibits an extremely tight circalunar circadian behavior that results in an impressive bioluminescent mating swarm, thought to be due to a conventional luciferase-mediated oxidation of a light-emitting luciferin. In addition, the four eyes become hypertrophied and heavily pigmented, and the nephridial system is modified to store and release gametes and associated secretions. In an effort to elucidate transcripts related to bioluminescence, circadian or circalunar periodicity, as well as epitoky-related changes of the eyes and nephridial system, we examined the transcriptomic profile of three female O. enopladuring a bioluminescent swarm in Ferry Reach, Bermuda. …

Dual Graph Partitioning Highlights A Small Group Of Pseudoknot-Containing Rna Submotifs, Swati Jain, Cigdem S. Bayrak, Louis Petingi, Tamar Schlick

Publications and Research

RNA molecules are composed of modular architectural units that define their unique structural and functional properties. Characterization of these building blocks can help interpret RNA structure/function relationships. We present an RNA secondary structure motif and submotif library using dual graph representation and partitioning. Dual graphs represent RNA helices as vertices and loops as edges. Unlike tree graphs, dual graphs can represent RNA pseudoknots (intertwined base pairs). For a representative set of RNA structures, we construct dual graphs from their secondary structures, and apply our partitioning algorithm to identify non-separable subgraphs (or blocks) without breaking pseudoknots. We report 56 subgraph blocks …

Lim Protein Ajuba Associates With The Rpa Complex Through Direct Cell Cycle-Dependent Interaction With The Rpa70 Subunit, Sandy Fowler, Pascal Maguin, Sampada Kalan, Diego Loayza

Publications and Research

DNA damage response pathways are essential for genome stability and cell survival. Specifically, the ATR kinase is activated by DNA replication stress. An early event in this activation is the recruitment and phosphorylation of RPA, a single stranded DNA binding complex composed of three subunits, RPA70, RPA32 and RPA14. We have previously shown that the LIM protein Ajuba associates with RPA, and that depletion of Ajuba leads to potent activation of ATR. In this study, we provide evidence that the Ajuba-RPA interaction occurs through direct protein contact with RPA70, and that their association is cell cycle-regulated and is reduced upon …

Translation Control By P53, Justina Kasteri, Dibash K. Das, Xuelin Zhong, Leah Persaud, Ashleigh Francis, Hilal Muharam, Moira Sauane

Publications and Research

The translation of mRNAs plays a critical role in the regulation of gene expression and therefore, in the regulation of cell proliferation, differentiation and apoptosis. Unrestricted initiation of translation causes malignant transformation and plays a key role in the maintenance and progression of cancers. Translation initiation is regulated by the ternary complex and the eukaryotic initiation factor 4F (eIF4F) complex. The p53 tumor suppressor protein is the most well studied mammalian transcription factor that mediates a variety of anti-proliferative processes. Post-transcriptional mechanisms of gene expression in general and those of translation in particular play a major role in shaping the …

Generating And Repairing Genetically Programmed Dna Breaks During Immunoglobulin Class Switch Recombination, Laura Nicolas, Montserrat Cols, Jee Eun Choi, Jayanta Chaudhuri

Publications and Research

Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR. Within the Ig …

Primordial Origin And Diversification Of Plasmids In Lyme Disease Agent Bacteria, Sherwood R. Casjens, Lia Di, Saymon Akther, Emmanuel F. Mongodin, Benjamin J. Luft, Steven E. Schutzer, Claire M. Fraser, Weigang Qiu

Publications and Research

Abstract

Background: With approximately one-third of their genomes consisting of linear and circular plasmids, the Lyme disease agent cluster of species has the most complex genomes among known bacteria. We report here a comparative analysis of plasmids in eleven Borreliella (also known as Borrelia burgdorferi sensu lato) species.

Results: We sequenced the complete genomes of two B. afzelii, two B. garinii, and individual B. spielmanii, B. bissettiae, B. valaisiana and B. finlandensis isolates. These individual isolates carry between seven and sixteen plasmids, and together harbor 99 plasmids. We report here a comparative analysis of these plasmids, along with 70 additional …

Data And Statistical Methods To Analyze The Human Microbiome, Levi Waldron

Publications and Research

The Waldron lab for computational biostatistics bridges the areas of cancer genomics and microbiome studies for public health, developing methods to exploit publicly available data resources and to integrate-omics studies.

The Candida Albicans Stress Response Gene Stomatin-Like Protein 3 Is Implicated In Ros-Induced Apoptotic-Like Death Of Yeast Phase Cells, Karen A. Conrad, Ronald Rodriguez, Eugenia C. Salcedo, Jason M. Rauceo

Publications and Research

The ubiquitous presence of SPFH (Stomatin, Prohibitin, Flotillin, HflK/HflC) proteins in all domains of life suggests that their function would be conserved. However, SPFH functions are diverse with organism-specific attributes. SPFH proteins play critical roles in physiological processes such as mechanosensation and respiration. Here, we characterize the stomatin ORF19.7296/SLP3 in the opportunistic human pathogen Candida albicans. Consistent with the localization of stomatin proteins, a Slp3p-Yfp fusion protein formed visible puncta along the plasma membrane. We also visualized Slp3p within the vacuolar lumen. Slp3p primary sequence analyses identified four putative S-palmitoylation sites, which may facilitate membrane localization and are conserved features …

Continuity Of Transcriptomes Among Colorectal Cancer Subtypes Based On Meta-Analysis, Siyuan Ma, Shuji Ogino, Princy Parsana, Reiko Nishihara, Zhirong Qian, Jeanne Shen, Kosuke Mima, Yohei Masugi, Yin Cao, Jonathan A. Nowak, Kaori Shima, Yujin Hoshida, Edward L. Giovannucci, Manish K. Gala, Andrew T. Chan, Charles S. Fuchs, Giovanni Parmigiani, Curtis Huttenhower, Levi Waldron

Publications and Research

Background: Previous approaches to defining subtypes of colorectal carcinoma (CRC) and other cancers based on transcriptomes have assumed the existence of discrete subtypes. We analyze gene expression patterns of colorectal tumors from a large number of patients to test this assumption and propose an approach to identify potentially a continuum of subtypes that are present across independent studies and cohorts.

Results: We examine the assumption of discrete CRC subtypes by integrating 18 published gene expression datasets and >3700 patients, and contrary to previous reports, find no evidence to support the existence of discrete transcriptional subtypes. Using a meta-analysis approach to …

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 …