Genetics and Genomics Commons^™

Mapping Regions Of Rnf168 Required For Its Degradation By Icp0, Andrea Cyr, Matthew Weitzman

e-Research: A Journal of Undergraduate Work

Viruses establish infection by overtaking host cell processes and developing mechanisms that promote viral replication. Herpes simplex virus undergoes lytic and latent cycles of infection throughout the lifespan of its host. The viral genome is transcriptionally silent during latency, but viral proteins are produced upon reactivation. Herpes simplex virus type 1 encodes the ICP0 protein, an E3 ubiquitin ligase required for reactivation from latency of the infectious virus. The immediate-early protein ICP0 regulates the herpes simplex virus by activating viral gene expression thereby initiating lytic infection. Cellular proteins are degraded by ICP0, promoting the virus to enter the lytic cycle. …

Haplotype Variety Analysis Of Human Populations: An Application To Hapmap Data, Michelle Creek, Cyril Rakovski

e-Research: A Journal of Undergraduate Work

We undertake a study to investigate the haplotype variety of distinct human populations. We use a natural measure of haplotype variety, the total number of haplotypes (TNH) present that reflects the number of haplotypes with nonzero frequencies estimated from the data at hand for each selection of multiple loci. For the analysis of real human populations, we use the haplotype data of the Denver Chinese, Tuscan Italians, Luhya Kenyans, and Gujarati Indians from release III of the HapMap database. Moreover, we show that the TNH statistic is biased in small sample data scenarios such as the HapMap and implement a …

On The Ranking Of The Disease Susceptibility Locus In Family-Based Candidate Gene Studies: A Simulation-Based Analysis, Lisa A. Brown, Cyril Rakovski

e-Research: A Journal of Undergraduate Work

The ranking of the p-value of the true causal single nucleotide polymorphism in the ordered list of individual SNP p-values is an important factor for achieving success in the ultimate objective of association studies - identifying deleterious genetic variants. Thus, we undertake a study to assess the implications of complex, multimarker correlation structure, sample size and disease models on the ranking of the causal SNP. We carry out an extensive family-based candidate gene simulation study to analyze the position of the disease susceptibility locus in the complete list of individual SNP p-values ordered according to their statistical significance. We simulate …

Rejuvenation Of Meiotic Cohesion In Oocytes During Prophase I Is Required For Chiasma Maintenance And Accurate Chromosome Segregation, Katherine A. Weng, Charlotte A. Jeffreys, Sharon E. Bickel

Dartmouth Scholarship

Chromosome segregation errors in human oocytes are the leading cause of birth defects, and the risk of aneuploid pregnancy increases dramatically as women age. Accurate segregation demands that sister chromatid cohesion remain intact for decades in human oocytes, and gradual loss of the original cohesive linkages established in fetal oocytes is proposed to be a major cause of age-dependent segregation errors. Here we demonstrate that maintenance of meiotic cohesion in Drosophila oocytes during prophase I requires an active rejuvenation program, and provide mechanistic insight into the molecular events that underlie rejuvenation. Gal4/UAS inducible knockdown of the cohesion establishment factor Eco …

Mammalian Keratin Associated Proteins (Krtaps) Subgenomes: Disentangling Hair Diversity And Adaptation To Terrestrial And Aquatic Environments, Imran Khan, Emanuel Maldonado, Vitor Vasconcelos, Stephen J. O'Brien, Warren E. Johnson, Agostinho Antunes

Marine & Environmental Sciences Faculty Articles

Background: Adaptation of mammals to terrestrial life was facilitated by the unique vertebrate trait of body hair, which occurs in a range of morphological patterns. Keratin associated proteins (KRTAPs), the major structural hair shaft proteins, are largely responsible for hair variation.

Results: We exhaustively characterized the KRTAP gene family in 22 mammalian genomes, confirming the existence of 30 KRTAP subfamilies evolving at different rates with varying degrees of diversification and homogenization. Within the two major classes of KRTAPs, the high cysteine (HS) subfamily experienced strong concerted evolution, high rates of gene conversion/recombination and high GC content. In contrast, high glycine-tyrosine …

The Genetic Interacting Landscape Of 63 Candidate Genes In Major Depressive Disorder: An Explorative Study, Magnus Lekman, Ola Hössjer, Peter Andrews, Henrik Källberg, Daniel Uvehag, Dennis Charney, Husseini Manji, John A. Rush, Frances J. Mcmahon, Jason H Moore, Ingrid Kockum

Dartmouth Scholarship

Background:

Genetic contributions to major depressive disorder (MDD) are thought to result from multiple genes interacting with each other. Different procedures have been proposed to detect such interactions. Which approach is best for explaining the risk of developing disease is unclear.

This study sought to elucidate the genetic interaction landscape in candidate genes for MDD by conducting a SNP-SNP interaction analysis using an exhaustive search through 3,704 SNP-markers in 1,732 cases and 1,783 controls provided from the GAIN MDD study. We used three different methods to detect interactions, two logistic regressions models (multiplicative and additive) and one data mining and …

Enhanced Expression Of Codon Optimized Mycobacterium Avium Subsp. Paratuberculosis Antigens In Lactobacillus Salivarius, Christopher D. Johnston, John P. Bannatine, Rodney Govender, Lorraine Endersen, Daniel Pletzer, Helge Weingart, Aidan Coffey, Jim O'Mahony, Roy D. Sleator

Department of Biological Sciences Publications

It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants …

Nsf Bets Big On David Angelini, Gerry Boyle

Colby Magazine

Something has been bugging Colby geneticist David Angelini.

How, Angelini wonders, can a single species (in this case the soapberry bug) produce two distinctly different forms, one with long wings and one with short, that are not linked to sex? What is the genetic mechanism that causes the wings to develop differently?

"Why does it not overshoot the long form? he asked. "Why doesn't it undershoot the short form? Why doesn't it end up somewhere in the middle? That's an open question."

And a question that the National Science Foundation wants him to answer.

A Homogenizing Process Of Selection Has Maintained An 'Ultra-Slow' Acetylation Nat2 Variant In Humans, Blandine Patillon, Pierre Luisi, Estella S. Poloni, Sotiria Boukouvala, Pierre Darlu, E. Genin, Audrey Sabbagh

Human Biology Open Access Pre-Prints

N-acetyltransferase 2 (NAT2) is an important enzyme involved in the metabolism of a wide spectrum of naturally occurring xenobiotics, including therapeutic drugs and common environmental carcinogens. Extensive polymorphism in NAT2 gives rise to a wide interindividual variation in acetylation capacity which influences individual susceptibility to various drug-induced adverse reactions and cancers. Striking patterns of geographic differentiation have been described for the main slow acetylation variants of the NAT2 gene, suggesting the action of natural selection at this locus. In the present study, we took advantage of the whole-genome sequence data available from the 1000 Genomes project to investigate the …

Hla Class Ii Alleles In The Otomi Population Of The Mezquital Valley. A Genetic Approach To The History Of Interethnic Migrations In The Mexican Central Plateau, Ana Itzel Juárez-Martín, Blanca Zoila González-Sobrino, Ángel Eduardo Camarena Olvera, Ramcés Falfán-Valencia

Human Biology Open Access Pre-Prints

From a historic and genetic point of view, the Otomi of the Mezquital Valley are a frontier people that have played an important role in the making of the population dynamics of the Mexican Central Plateau. Due to their antiquity in the area, the Otomi may be bearers of ancient genetic variability, shared mainly today with other groups belonging to the Otomanguean linguistic family and with the Nahua.

This study analyzes the HLA class II allele frequencies reported in Mexican indigenous populations, in order to provide an intra-regional level historical perspective of the genetic relationships between the Otomi of the …

Chlorovirus Skp1-Binding Ankyrin Repeat Protein Interplay And Mimicry Of Cellular Ubiquitin Ligase Machinery, Eric A. Noel, Ming Kang, Jiri Adamec, James L. Van Etten, George A. Oyler

James Van Etten Publications

The ubiquitin-proteasome system is targeted by many viruses that have evolved strategies to redirect host ubiquitination machinery. Members of the genus Chlorovirus are proposed to share an ancestral lineage with a broader group of related viruses, nucleo-cytoplasmic large DNA viruses (NCLDV). Chloroviruses encode an Skp1 homolog and ankyrin repeat (ANK) proteins. Several chlorovirus-encoded ANK repeats contain C-terminal domains characteristic of cellular F-boxes or related NCLDV chordopox PRANC (pox protein repeats of ankyrin at C-terminal) domains. These observations suggested that this unique combination of Skp1 and ANK repeat proteins might form complexes analogous to the cellular Skp1-Cul1-F-box (SCF) ubiquitin ligase complex. …

Estimating Migration Rates Between Populations Of Zostera Marina In The San Francisco Bay, Elizabeth S. Gutierrez

STAR Program Research Presentations

Eelgrass (Zostera marina) is a highly clonal marine angiosperm that can also reproduce sexually through flowering and seed formation. In a previous study, Fst values from six microsatellite loci suggested that a perennial San Francisco Bay subpopulation at Point Molate (Richmond, California) was able to recover from a drastic 2006 die-off through seed recruitment from neighboring eelgrass subpopulations, changing its reproductive strategy from clonal to sexual. Although Fst measures continue to be widely used in population genetics, the assumptions under which they operate are not always appropriate given certain circumstances, such small population sizes and/or asymmetrical migration rates. Our summer …

Long-Term Cre-Mediated Retrograde Tagging Of Neurons Using A Novel Recombinant Pseudorabies Virus, Hysell V. Oviedo, Hassasna K. Oyibo, Petr Znamenskiy, Lynn W. Enquist, Anthony M. Zador

Publications and Research

Brain regions contain diverse populations of neurons that project to different long-range targets. The study of these subpopulations in circuit function and behavior requires a toolkit to characterize and manipulate their activity in vivo. We have developed a novel set of reagents based on Pseudorabies Virus (PRV) for efficient and long-term genetic tagging of neurons based on their projection targets. By deleting IE180, the master transcriptional regulator in the PRV genome, we have produced a mutant virus capable of infection and transgene expression in neurons but unable to replicate in or spread from those neurons. IE180-null mutants showed no cytotoxicity, …

Endogenous Retrovirus Insertion In The Kit Oncogene Determines White And White Spotting In Domestic Cats, Victor A. David, Marilyn Menotti-Raymond, Andrea Coots Wallace, Melody E. Roelke, James Kehler, Robert Leighty, Eduardo Eizirik, Steven S. Hannah, George Nelson, Alejandro A. Schaffer, Catherine J. Connelly, Stephen J. O'Brien, David K. Ryugo

Biology Faculty Articles

The Dominant White locus (W) in the domestic cat demonstrates pleiotropic effects exhibiting complete penetrance for absence of coat pigmentation and incomplete penetrance for deafness and iris hypopigmentation. We performed linkage analysis using a pedigree segregating White to identify KIT (Chr. B1) as the feline W locus. Segregation and sequence analysis of the KIT gene in two pedigrees (P1 and P2) revealed the remarkable retrotransposition and evolution of a feline endogenous retrovirus (FERV1) as responsible for two distinct phenotypes of the W locus, Dominant White, and white spotting. A full-length (7125 bp) FERV1 element is associated with white …

The Trehalose Pathway In Maize: Conservation And Gene Regulation In Response To The Diurnal Cycle And Extended Darkness, Clémence Henry, Samuel W. Bledsoe, Allison Siekman, Alec Kollman, Brian M. Waters, Regina Feil, Mark Stitt, L. Mark Lagrimini

Department of Agronomy and Horticulture: Faculty Publications

Energy resources in plants are managed in continuously changing environments, such as changes occurring during the day/night cycle. Shading is an environmental disruption that decreases photosynthesis, compromises energy status, and impacts on crop productivity. The trehalose pathway plays a central but not well-defined role in maintaining energy balance. Here, we characterized the maize trehalose pathway genes and deciphered the impacts of the diurnal cycle and disruption of the day/night cycle on trehalose pathway gene expression and sugar metabolism. The maize genome encodes 14 trehalose-6-phosphate synthase (TPS) genes, 11 trehalose-6-phosphate phosphatase (TPP) genes, and one trehalase gene. Transcript abundance of most …

Population Genetic Structure Of Traditional Populations In The Peruvian Central Andes And Implications For South American Population History, Graciela S. Cabana, Cecil M. Lewis, Jr., Raúl Y. Tito, R. Alan Covey, Angela M. Cáceres, C. Leslie Castillo Pampas, Augusto F. De La Cruz, Diana Durand, Genevieve Housman, Brannon I. Hulsey, Gian Carlo Iannacone, Paul W. Lopez, Rolando Martínez, Ángel Medina, Olimpio Ortega Dávila, Karla Paloma Osorio Pinto, Susan I. Polo Santillán, Percy Rojas Domínguez, Meagan Rubel, Heather F. Smith, Silvia E. Smith, Verónica Rubín De Celis, Beatriz Lizárraga, Anne C. Stone

Human Biology Open Access Pre-Prints

Molecular-based characterizations of Andean peoples are traditionally conducted in the service of elucidating continental-level evolutionary processes in South America. Consequently, “western” Andean population genetic variation is often represented in relation to “eastern” variation among Amazon and Orinoco River Basin populations. This west-east contrast in patterns of population genetic variation is typically attributed to large-scale phenomena, such as dual founder colonization events and/or differing long-term microevolutionary histories. However, alternative explanations that consider the nature and causes of population genetic diversity within the Andean region remain underexplored.

Here we examine population genetic diversity in the Peruvian Central Andes using mtDNA HVI and …

De Novo Assembly Of The Common Marmoset Transcriptome From Nextgen Mrna Sequences, Mnirnal D. Maudhoo, Dongren Ren, Julien S. Gradnigo, Robert M. Gibbs, Austin C. Lubker, Etsuko N. Moriyama, Jeffrey French, Robert B. Norgren

Psychology Faculty Publications

Background: Nonhuman primates are important for both biomedical studies and understanding human evolution. Although research in these areas has mostly focused on Old World primates, such as the rhesus macaque, the common marmoset (Callithrix jacchus), a New World primate, offers important advantages in comparison to other primates, such as an accelerated lifespan. To conduct Next Generation expression studies or to study primate evolution, a high quality annotation of the marmoset genome is required. The availability of marmoset transcriptome data from five tissues, including both raw sequences and assembled transcripts, will aid in the annotation of the newly …

Nack Is An Integral Component Of The Notch Transcriptional Activation Complex And Is Critical For Development And Tumorigenesis, Kelly L Weaver, Marie-Clotilde Alves-Guerra, Ke Jin, Zhiqiang Wang, Xiaoqing Han, Prathibha Ranganathan, Xiaoxia Zhu, Thiago Dasilva, Wei Liu, Francesca Ratti, Renee M Demarest, Cristos Tzimas, Meghan Rice, Rodrigo Vasquez-Del Carpio, Nadia Dahmane, David J Robbins, Anthony J Capobianco

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The Notch signaling pathway governs many distinct cellular processes by regulating transcriptional programs. The transcriptional response initiated by Notch is highly cell context dependent, indicating that multiple factors influence Notch target gene selection and activity. However, the mechanism by which Notch drives target gene transcription is not well understood. Herein, we identify and characterize a novel Notch-interacting protein, Notch activation complex kinase (NACK), which acts as a Notch transcriptional coactivator. We show that NACK associates with the Notch transcriptional activation complex on DNA, mediates Notch transcriptional activity, and is required for Notch-mediated tumorigenesis. We demonstrate that Notch1 and NACK are …

Rapid Method Of Processing Sperm For Nucleic Acid Extraction In Clinical Research, Matthew K. De Gannes

Masters Theses

Background: Sperm contain highly compact nuclei, inhibiting DNA extraction using traditional techniques. Current methods extracting sperm DNA involve lengthy lysis and no means of stabilizing DNA, hindering clinical research.

Objective: We sought to optimize an efficient method of extracting high quality human sperm DNA.

Methods: Sperm from three volunteers were isolated using PureCeption. We tested 1) proteinase K with DNA/RNA Shield, 2) DTT and TCEP as reducing agents, 3) QIAshredder homogenization, and 4) stability of sperm DNA fresh (baseline) or after 4 weeks of storage at 4^OC in DNA/RNA Shield using modified Quick-gDNA MiniPrep. DNA was PCR amplified …

Orthoclust: An Orthology-Based Network Framework For Clustering Data Across Multiple Species, Koon-Kiu Yan, Daifeng Wang, Joel Rozowsky, Henry Zheng, Chao Cheng, Mark Gerstein Gerstein

Dartmouth Scholarship

Increasingly, high-dimensional genomics data are becoming available for many organisms.Here, we develop OrthoClust for simultaneously clustering data across multiple species. OrthoClust is a computational framework that integrates the co-association networks of individual species by utilizing the orthology relationships of genes between species. It outputs optimized modules that are fundamentally cross-species, which can either be conserved or species-specific. We demonstrate the application of OrthoClust using the RNA-Seq expression profiles of Caenorhabditis elegans and Drosophila melanogaster from the modENCODE consortium. A potential application of cross-species modules is to infer putative analogous functions of uncharacterized elements like non-coding RNAs based on guilt-by-association.