Genetics and Genomics Commons^™

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 …

Integration Of Bmp And Insulin/Igf-1 Signaling Regulates Multiple Homeostatic Functions In Caenorhabditis Elegans, James F. Clark

Dissertations, Theses, and Capstone Projects

The maintenance of homeostatic functions is key to the survival and well-being of an organism. Regulation of homeostasis relies on varied inputs, both intrinsic and extrinsic, to potentiate a web of interconnected signaling relays. Insulin/IGF-1 signaling (IIS) is a well-known regulator of glucose and lipid metabolism, as well as having far reaching effects in other homeostatic mechanisms. On the other hand, bone morphogenetic protein (BMP), a member of the transforming growth factor beta signaling superfamily, is known for its role in differentiation and development, with only recent studies highlighting potential roles in metabolic homeostasis. Here we elucidate new functions for …

Underlying Contribution Of Executive Functioning To Cognition And Academic Achievement In Individuals With Dystrophinopathy, Robert Fee

Dissertations, Theses, and Capstone Projects

Dystrophinopathy is a genetic disorder that results in the lack of or abnormal expression of the protein dystrophin. It is a disorder that alters cell structure and function, impacts the developing brain and brain function, presents with multi-domain cognitive deficits, and influences both mood and behavior. Cognitive impairments appear to be more localized to specific areas of functioning rather than a global deficit; however, deficits have been identified across multiple cognitive domains including language and aspects of executive functioning. A careful examination of the cognitive phenotype and its association to mutations affecting CNS isoforms is necessary to clarify the neuropsychological …

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 …

A Contribution Toward A Global Monograph Of Gyroporus: Taxonomy, Phylogeny, Biogeography, Naveed Davoodian

Dissertations, Theses, and Capstone Projects

Gyroporus (Sclerodermatineae, Boletales, Agaricomycetes, Basidiomycota, Fungi) is a genus of ectomycorrhizal mushroom-forming fungi distributed throughout the world in suitable habitats. Previous attempts to untangle the diversity of this genus proved difficult due to the presence of semi-cryptic species and equivocal results from phylogenetic analysis of ribosomal RNA markers. To overcome these obstacles, a combined taxonomic and phylogenetic (emphasizing protein-coding genes) approach is used here to delimit species and elucidate geographic and evolutionary patterns of Gyroporus. Careful study of relevant literature and herbarium specimens was augmented by field work in North America, Australia, and East Asia for observation and collection …

Using Molecular Markers To Trace The Population History Of Volant Organisms At Differing Temporal Scales, Noah A. Burg

Dissertations, Theses, and Capstone Projects

Using molecular markers to test phylogenetic and phylogeographic hypotheses is critical for tracking the population origin of invasive, introduced species (Chapter 2, Chapter 4) and to identify the systematic relationships of disparate lineages at both shallow and deep evolutionary time scales (Chapters 3, Chapter 4). In this thesis, Sanger Sequencing was used to generate datasets based on fresh and preserved tissue from specimens collected in the field, as well as museum tissue vouchers granted from various institutions in the US and Europe. In combining these source materials, data were generated for three focal studies: 1) In the first research section …

Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek

Dissertations, Theses, and Capstone Projects

Escherichia coli is a well-known pathogen, and importantly, a widely used model organism in all fields of biological sciences for cloning, protein purification, and as a model for Gram-negative bacterial species. And yet, researchers do not fully understand how this bacterium replicates and divides. Every year additional division proteins are discovered, which adds complexity to how we understand E. coli undergoes cell division. Due to their specific roles in cytokinesis, some of these proteins may be potential targets for development of antibacterials or bacteriostatics, which are much needed for fighting the current global antibacterial deficit. My thesis work focuses on …

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 …

Genetic Basis Of Larval Crystal Cell Quantity Variation In The Drosophila Genetic Reference Panel (Dgrp), Brian Tang

Student Theses and Dissertations

Crystal cells are one of three requisite hemocytes that take part in fighting infection and wound healing in Drosophila melanogaster (common fruit flies). The developmental genetics of crystal cell formation is only beginning to be discovered. To address this question, we performed a Genome-Wide Association Study (GWAS) on larval crystal cell number from 78 isolines of the Drosophila Genetic Reference Panel (DGRP) collection. The DGRP consists of naturally caught fruit flies that are inbred to near homozygosity with completely sequenced genomes. By placing the wandering third instar larvae under heatshock, a process that induces the melanization of crystal cells, …

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 …

Manipulation Of Ploidy In Caenorhabditis Elegans, Erlyana K. Clarke, Katherine A. Rivera Gomez, Zaki Mustachi, Mikaela C. Murph, Mara Schvarzstein

Advanced Science Research Center

Mechanisms that involve whole genome polyploidy play important roles in development and evolution; also, an abnormal generation of tetraploid cells has been associated with both the progression of cancer and the development of drug resistance. Until now, it has not been feasible to easily manipulate the ploidy of a multicellular animal without generating mostly sterile progeny. Presented here is a simple and rapid protocol for generating tetraploid Caenorhabditis elegans animals from any diploid strain. This method allows the user to create a bias in chromosome segregation during meiosis, ultimately increasing ploidy in C. elegans. This strategy relies on the transient …

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 …

Convergent Evolution Of Biochemical Innovations In Polychaetes: Characterizing The Molecular Basis Of Bioluminescence And Venom Production, Aida E. Verdes Gorín

Dissertations, Theses, and Capstone Projects

The convergent evolution of phenotypic traits is a widespread phenomenon across the tree of life and is explained as the outcome of different taxa facing similar selective forces or environmental conditions. A longstanding question in evolutionary biology is whether the evolution of convergent phenotypes in unrelated lineages is driven by similar or different molecular processes. The research presented here investigates this question by characterizing the molecular basis of two biochemical innovations, bioluminescence and venom production, that have evolved independently in different lineages of polychaetes worms (Annelida). We use an integrative approach, combining next-generation sequencing, phylogenetics and computational tools to evaluate …

Bio2450l Genetics Laboratory Manual, Christopher Blair

Open Educational Resources

No abstract provided.

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 …