Genetics and Genomics Commons^™

Genetic Sex Conditions And Redefining Sex, Jayce O'Shields

Student Scholarship

Western culture has a tendency to value binaries and discreet categories that separate its social structure and provide a sense of order and organization. The value placed on binaries and categories may be advantageous in some aspects, but when it starts to infringe upon the legal and medical rights of individuals not easily placed in either binary category, it can become less advantageous.

A baby is usually classified as either male or female shortly after birth, and all future legal, social, and economic actions and rights of that individual are more or less decided according to this classification. A problem …

Novel Neuroprotective Function Of Apical-Basal Polarity Genecrumbs In Amyloid Beta 42 (Aβ42) Mediated Neurodegeneration, Andrew Steffensmeier, Meghana Tare, Oorvashi Roy Puli, Rohan Modi, Jaison Nainaparampil, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

Alzheimer's disease (AD, OMIM: 104300), a progressive neurodegenerative disorder with no cure to date, is caused by the generation of amyloid-beta-42 (Aβ42) aggregates that trigger neuronal cell death by unknown mechanism(s). We have developed a transgenic Drosophilaeye model where misexpression of human Aβ42 results in AD-like neuropathology in the neural retina. We have identified an apical-basal polarity gene crumbs (crb) as a genetic modifier of Aβ42-mediated-neuropathology. Misexpression of Aβ42 caused upregulation of Crb expression, whereas downregulation of Crb either by RNAi or null allele approach rescued the Aβ42-mediated-neurodegeneration. Co-expression of full length Crb with Aβ42 increased severity of Aβ42-mediated-neurodegeneration, …

Identification Of Set1 Target Genes, William Beyer, Scott D. Briggs

The Summer Undergraduate Research Fellowship (SURF) Symposium

The Set1 complex, a histone methyltransferase complex found in S. cerevisiae (budding yeast), is the only histone methyltransferase responsible for catalyzing methylation of histone H3 at Lysine 4. It possesses homologues in other species, humans included. While yeast only have the Set1 complex, the human homologues of the yeast Set1 complex include mixed-lineage leukemia family (MLL1-4), Set1 A, Set1 B, among others. MLL1-4 has been shown to play a role in transcription, cell type specification, and the development of leukemia. One application of characterizing the role of a protein is that the information gained can provide insight into the function …

Evaluation Of Higher Plant Virus Resistance Genes In The Green Alga, Chlorella Variabilis Nc64a, During The Early Phase Of Infection With Paramecium Bursaria Chlorella Virus-1, Janet M. Rowe, David D. Dunigan, Guillaume Blanc, James R. Gurnon, Yuannan Xia, James L. Van Etten

David D Dunigan Ph. D.

With growing industrial interest in algae plus their critical roles in aquatic systems, the need to understand the effects of algal pathogens is increasing. We examined a model algal host–virus system, Chlorella variabilis NC64A and virus, PBCV-1. C. variabilis encodes 375 homologs to genes involved in RNA silencing and in response to virus infection in higher plants. Illumina RNA-Seq data showed that 325 of these homologs were expressed in healthy and early PBCV-1 infected (≤60 min) cells. For each of the RNA silencing genes to which homologs were found, mRNA transcripts were detected in healthy and infected cells. C. variabilis, …

Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass

Aaron P Blaisdell

Welcome to the first issue of the Journal of Evolution and Health! The Journal of Evolution and Health is the peer-reviewed, open-access journal of the Ancestral Health Society, a community of scientists, healthcare professionals, and laypersons who collaborate to understand health challenges from an evolutionary perspective.

Function Of A Novel Checkpoint Protein In The Germ Line, Steven Drellishak, Marina Bykova, G. Valentin Börner

Undergraduate Research Posters 2013

Successful reproduction of Saccharomyces cerevisiae relies on the organism’s ability to complete the meiotic cell cycle and produce viable gametes. Zip1 is a protein that constitutes the central component of a protein structure that connects homologous chromosomes known as the synaptonemal complex. Zip1 is important for progression through the meiotic cell cycle. The C terminus of the coiled-coil Zip 1 protein is responsible for localization to the axes of the chromosomes. An internal deletion near the C terminus of Zip1, called zip1-c1, yields a stronger meiotic arrest than a mutation where Zip1 is completely deleted. The more efficient meiotic progression …

Hypothesis Driven Single Nucleotide Polymorphism Search (Hydn-Snp-S), Rebecca J. Swett, Angela Elias, Jeffrey A. Miller, Gregory E. Dyson, G. AndréS Cisneros

Chemistry Faculty Research Publications

The advent of complete-genome genotyping across phenotype cohorts has provided a rich source of information for bioinformaticians. However the search for SNPs from this data is generally performed on a study-by-study case without any specific hypothesis of the location for SNPs that are predictive for the phenotype. We have designed a method whereby very large SNP lists (several gigabytes in size), combining several genotyping studies at once, can be sorted and traced back to their ultimate consequence in protein structure. Given a working hypothesis, researchers are able to easily search whole genome genotyping data for SNPs that link genetic locations …

Draft Genome Sequence Of A Stable Mucoid Strain Of Pseudomonas Aeruginosa Pao581 With A Muca25 Mutation, Yeshi Yin, T. Ryan Withers, John R. W. Govan, Shannon L. Johnson, Hongwei D. Yu

Biochemistry and Microbiology

A mutation in the mucA gene, which encodes a negative regulator of alginate production in Pseudomonas aeruginosa, is the main mechanism underlying the conversion to mucoidy in clinical isolates from patients with cystic fibrosis (CF). Here, we announce the draft genome sequence of the stable alginate-overproducing mucoid strain P. aeruginosa PAO581 with a mucA25 mutation, a derivative from the nonmucoid strains P. aeruginosa PAO381 and PAO1.

Coupling S100a4 To Rhotekin Alters Rho Signaling Output In Breast Cancer Cells, Min Chen, Anne R. Bresnick, Kathleen L. O'Connor

Markey Cancer Center Faculty Publications

Rho signaling is increasingly recognized to contribute to invasion and metastasis. In this study, we discovered that metastasis-associated protein S100A4 interacts with the Rho-binding domain (RBD) of Rhotekin, thus connecting S100A4 to the Rho pathway. Glutathione S-transferase pull-down and immunoprecipitation assays demonstrated that S100A4 specifically and directly binds to Rhotekin RBD, but not the other Rho effector RBDs. S100A4 binding to Rhotekin is calcium-dependent and uses residues distinct from those bound by active Rho. Interestingly, we found that S100A4 and Rhotekin can form a complex with active RhoA. Using RNA interference, we determined that suppression of both S100A4 and …

Chromatin Insulators: Master Regulators Of The Eukaryotic Genome, Todd Andrew Schoborg

Doctoral Dissertations

Proper organization of the chromatin fiber within the three dimensional space of the eukaryotic nucleus relies on a number of DNA elements and their interacting proteins whose structural and functional consequences exert significant influence on genome behavior. Chromatin insulators are one such example, where it is thought that these elements assist in the formation of higher order chromatin loop structures by mediating long-range contacts between distant sites scattered throughout the genome. Such looping serves a dual role, helping to satisfy both the physical constraints needed to package the linear DNA polymer within the small volume of the nucleus while simultaneously …

The Importance Of Epigenetic Phenomena In Regulating Activity Of The Genetic Material, Sin Chan

Senior Honors Projects

Genetics has taught us that genes are represented as discrete sequences within a larger DNA molecule found embedded within the chromosomes of a living cell. Collectively these chromosomes and their associated genes carry all of the instructions for life. Until recently, the prevailing thought has been that genes are destiny in the life of an individual since the genes carry the information that determines the general traits and characteristics associated with that individual. The relatively recent understanding of mechanisms that underlie epigenetic phenomena has led to a rethinking of this concept. Epigenetics describes cellular mechanisms that explain how two individuals …

Med13p Prevents Stress-Independent Mitochondrial Hyperfragmentation And Aberrant Apoptosis Activation In Saccharomyces Cerevisiae By Controlling Cyclin C Nuclear Localization, Svetlana Khakhina

Graduate School of Biomedical Sciences Theses and Dissertations

During aging, and as a result of environmental changes, cells are exposed to elevated levels of reactive oxygen species (ROS). High ROS levels induce lipid oxidation, protein aggregation, mitochondrial hyperfragmentation, DNA damage and programmed cell death (PCD), also called apoptosis. PCD is a highly regulated process and its misregulation has been linked to neurodegenerative diseases and cancer development.

Our hypothesis is that cyclin C plays a role in the initiation of apoptosis. During normal conditions, cyclin C represses the transcription of stress response genes (SRG). In response to stress, cyclin C translocates to the cytoplasm where it facilitates mitochondrial hyperfragmentation …

Recurrent Modification Of A Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity, William A. Rogers, Joseph R. Salomone, David J. Tacy, Eric M. Camino, Kristen A. Davis, Mark Rebeiz, Thomas M. Williams

Biology Faculty Publications

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. InDrosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development …

Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu

Biochemistry and Microbiology

Pseudomonas aeruginosa is a Gram negative, opportunistic pathogen that uses the overproduction of alginate, a surface polysaccharide, to form biofilms in vivo. Overproduction of alginate, also known as mucoidy, affords the bacterium protection from the host's defenses and facilitates the establishment of chronic lung infections in individuals with cystic fibrosis. Expression of the alginate biosynthetic operon is primarily controlled by the alternative sigma factor AlgU (AlgT/σ²²). In a nonmucoid strain, AlgU is sequestered by the transmembrane antisigma factor MucA to the cytoplasmic membrane. AlgU can be released from MucA via regulated intramembrane proteolysis by proteases AlgW and MucP …

Characterization Of Aebp2 Mutant Mice, Arundhati Bakshi

Honors Theses

No abstract provided.

Development And Application Of Mass Spectrometry-Based Proteomics To Generate And Navigate The Proteomes Of The Genus Populus, Paul Edward Abraham

Doctoral Dissertations

Historically, there has been tremendous synergy between biology and analytical technology, such that one drives the development of the other. Over the past two decades, their interrelatedness has catalyzed entirely new experimental approaches and unlocked new types of biological questions, as exemplified by the advancements of the field of mass spectrometry (MS)-based proteomics. MS-based proteomics, which provides a more complete measurement of all the proteins in a cell, has revolutionized a variety of scientific fields, ranging from characterizing proteins expressed by a microorganism to tracking cancer-related biomarkers. Though MS technology has advanced significantly, the analysis of complicated proteomes, such as …

Functional Analysis Of A Putative Membrane-Bound Endo-Β-1,4-Glucanase From Panicum Virgatum, Joshua N Grant, Jonathan D. Willis, Neal Stewart

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Cellulose is the most abundant carbohydrate in the world and is degraded by the synergistic action of multiple enzymes. One large family of enzymes capable of hydrolyzing cellulose is glycoside hydrolase family 9 (GH9), which includes several endoglucanases. Recent research into the molecular biology of plants has revealed certain genes coding for endo-β-1,4-glucanases (EGases). The EGases in plants are primarily functional during cell elongation through wall stress relaxation. GH9 enzymes have been found in insects, bacteria, oomycetes, and fungi. In insects, EGases enable the organism to digest cellulose; in fungi, EGases are suspected to play an important role in obtaining …

Human-Specific Histone Methylation Signatures At Transcription Start Sites In Prefrontal Neurons, Hennady P. Shulha, Jessica L. Crisci, Denis Reshetov, Jogender S. Tushir, Iris Cheung, Rahul Bharadwaj, Hsin-Jung Chou, Isaac B. Houston, Cyril J. Peter, Amanda C. Mitchell, Wei-Dong Yao, Richard H. Myers, Jiang-Fan Chen, Todd M. Preuss, Evgeny I. Rogaev, Jeffrey D. Jensen, Zhiping Weng, Schahram Akbarian

Jessica L Crisci

Cognitive abilities and disorders unique to humans are thought to result from adaptively driven changes in brain transcriptomes, but little is known about the role of cis-regulatory changes affecting transcription start sites (TSS). Here, we mapped in human, chimpanzee, and macaque prefrontal cortex the genome-wide distribution of histone H3 trimethylated at lysine 4 (H3K4me3), an epigenetic mark sharply regulated at TSS, and identified 471 sequences with human-specific enrichment or depletion. Among these were 33 loci selectively methylated in neuronal but not non-neuronal chromatin from children and adults, including TSS at DPP10 (2q14.1), CNTN4 and CHL1 (3p26.3), and other neuropsychiatric susceptibility …

Long-Term Data For Endemic Frog Genera Reveal Potential Conservation Crisis In The Bale Mountains, Ethiopia, David J. Gower, Roman K. Aberra, Silvia Schwaller, Malcolm J. Largen, Ben Collen, Stephen Spawls, Michele Menegon, Breda M. Zimkus, Rafael O. De Sá, Et Al.

Biology Faculty Publications

Populations of many frogs have declined alarmingly in recent years, placing nearly one third of the > 6,000 species under threat of extinction. Declines have been attributed largely to habitat loss, environmental degradation and/or infectious diseases such as chytridiomycosis. Many frogs undergo dramatic natural population fluctuations such that long-term data are required to determine population trends without undue influence of stochastic factors. We present long-term quantitative data (individuals encountered per person hour of searching) for four monotypic frog genera endemic to an Afromontane region of exceptional importance but growing conservation concern: one endemic to the Ethiopian highlands (Spinophrynoides osgoodi) and three …

Global Neuroaids Roundtable, Jeymohan Joseph, Cristian L. Achim, Michael J. Boivin, Bruce J. Brew, David B. Clifford, Deborah A. Colosi, Ronald J. Ellis, Robert K. Heaton, Amadou Gallo-Diop, Igor Grant, Georgette D. Kanmogne, Mahendra Kumar, Scott Letendre, Thomas D. Marcotte, Avindra Nath, Carlos A. Pardo, Robert H. Paul, Lynn Pulliam, Kevin Robertson, Walter Royal Iii, Ned Sacktor, Pasiri Sithinamsuwan, Davey M. Smith, Victor Valcour, Brian Wigdahl, Charles Wood

Nebraska Center for Virology: Faculty Publications

In May 2012, the Division of AIDS Research at the National Institute of Mental Health (NIMH) organized the “Global NeuroAIDS Roundtable” in conjunction with the 11th International Symposium on Neurovirology and the 2012 Conference on HIV in the Nervous System. The meeting was held in New York, NY, USA and brought together NIMH-funded investigators who are currently working on projects related to the neurological complications of AIDS (NeuroAIDS) in Africa, Asia, Eastern Europe, and Latin America in order to provide an opportunity to share their recent findings and discuss the challenges encountered within each country. The major goals of the …

Molecular Architecture Of The Uncleaved Hiv-1 Envelope Glycoprotein Trimer, Youdong Mao, Luis Castillo-Menendez, Liping Wang, Christopher Gu, Alon Herschhorn, Anik Désormeaux, Andrés Finzi, Shi-Hua Xiang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer, a membrane-fusing machine, mediates virus entry into host cells and is the sole virusspecific target for neutralizing antibodies. Binding the receptors, CD4 and CCR5/CXCR4, triggers Env conformational changes from the metastable unliganded state to the fusion-active state. We used cryo-electron microscopy to obtain a 6-Å structure of the membranebound, heavily glycosylated HIV-1 Env trimer in its uncleaved and unliganded state. The spatial organization of secondary structure elements reveals that the unliganded conformations of both gp120 and gp41 subunits differ from those induced by receptor binding. The gp120 trimer association domains, which …

Examining The Functional Role Of Dprl-1 In Drosophila Melanogaster, John Valenzuela

Summer Research

The Phosphatase of Regenerating Liver (PRL) family of proteins control cell growth, motility and proliferation. They have been shown to elevate the levels of these functions, leading to an increase in cancer metastasis (“malignancy”), when they are overexpressed. The goal of this experiment is to knockout PRL gene expression to examine the general function of PRL proteins. Drosophila melanogaster have only one copy of the PRL gene (dPRL-1), as opposed to humans and other mammals, which have 3. Thus, using P-element imprecise excision to create mutant strains either fully lacking or with decreased function of the dPRL-1 protein, …

Comparison Of Th1 Cytokines And T Cell Markers Gene Expressions Between Virulent And An Attenuated Eiav Vaccine Strain, Talia R. Henkle

Lewis Honors College Capstone Collection

The equine infectious anemia virus (EIAV) is closely related to HIV and has been used as a model to identify protective mechanisms against lentivirus infection. In horses, EIA infection progresses for about a year before infected horses manage to control virus replication. This naturally-gained protection is absolutely dependent on active immune responses as evidenced by the fact that immunosuppressive drugs can induce the recurrence of disease. As the resolution of initial viremia correlates with the appearance of virus specific cytotoxic T lymphocytes (CTL), we believe that cellular immune responses play a key role in controlling EIAV in the horse. In …

A Path To Success? A Review Of Evolution, Development, And The Predictable Genome By David L. Stern, Hope Hollocher, Charles H. Pence, Grant Ramsey, Michelle M. Wirth

Faculty Publications

No abstract provided.

The New Frontier Of Advanced Reproductive Technology: Reevaluating Modern Legal Parenthood, Yehezkel H. Margalit Dr., John D. Loike Dr., Orrie Levy Adv.

Hezi Margalit

Assisted reproductive technologies (ARTs) have challenged our deepest conceptions of what it means to be a parent by fragmenting traditional aspects of parenthood. The law has been slow to respond to this challenge, and numerous academic articles have proposed models for adapting parentage laws to ARTs. In the coming years, however, scientific advancements in reproductive technologies, such as somatic cell nuclear transfer and stem cell technologies, will challenge both parentage laws and proposed legal models for traditional ARTs in new and fascinating ways. For instance, these advanced technologies could allow two women to create a child without any male genetic …

Gene Transfer In A Newly Established Spontaneous Feline Fibrosarcoma Cell Line, Rounak Nande

Theses, Dissertations and Capstones

Fibrosarcoma is a deadly disease in cats and is most often located at classical vaccine injections sites. More rare forms of spontaneous non-vaccination site (NSV) fibrosarcomas have been described and have been found associated to genetic alterations.

Purpose of this study was to compare the efficacy of adenoviral gene therapy in NVS fibrosarcoma. The NVS fibrosarcoma cell line (Cocca-6A) was isolated from a spontaneous fibrosarcoma that occurred in a domestic calico cat. Cocca-6A fibrosarcoma cells were morphologically and cytogenetically characterized. The feline cells were karyotyped and their chromosome number was counted using a Giemsa staining. Giemsa block staining of metaphase …

Changes In Cell Morphology And The Cellular Localization Of Protein Kinase Dsk1 In Schizosaccharomyces Pombe In Response To Butylated Hydroxyanisole, Jacqueline T. Humphries

Scripps Senior Theses

Dsk1 is the Schizosaccharomyces pombe functional homolog of human SRPK1, an SR protein kinase that regulates localization and function of SR protein splicing factors involved in transcription, alternative splicing, and mRNA export. It has been shown that a Dsk1 deletion strain of S. pombe is sensitive to exposure to butylated hydroxyanisole (BHA), a phenol derivative commonly used as a food preservative. Little is known about how BHA interacts with cells on a functional level, although it has been shown to be cytotoxic and tumorigenic. The aims of this thesis are to study the effect of BHA on eukaryotic cells and …

Early Childhood Infection Of Kaposi’S Sarcoma-Associated Herpesvirus In Zambian Households: A Molecular Analysis, Landon Olp, Danielle M. Shea, Maxine K. White, Clement Gondwe, Chipepo Kankasa, Charles Wood

Nebraska Center for Virology: Faculty Publications

Sub-Saharan Africa is endemic for Kaposi’s sarcoma-associated herpesvirus (KSHV) and there is a high rate of early childhood infection; however, the transmission sources are not well characterized. We examined household members as potential KSHV transmission sources to young children in the KSHV-endemic country of Zambia. To this end, we enrolled and followed Zambian households with at least one KSHV-seropositive child and collected longitudinal buccal swab samples. KSHV burden was evaluated and K1 sequences from the children were determined and analyzed for differences to K1 sequences from household members. The K1 sequences were also analyzed for evolution over time. We generated …

Towards Defining The Chloroviruses: A Genomic Journey Through A Genus Of Large Dna Viruses, Adrien Jeanniard, David D. Dunigan, James Gurnon, Irina V. Agarkova, Ming Kang, Jason Vitek, Garry Duncan, O William Mcclung, Megan Larsen, Jean-Michel Claverie, James L. Van Etten, Guillaume Blanc

Nebraska Center for Virology: Faculty Publications

Background: Giant viruses in the genus Chlorovirus (family Phycodnaviridae) infect eukaryotic green microalgae. The prototype member of the genus, Paramecium bursaria chlorella virus 1, was sequenced more than 15 years ago, and to date there are only 6 fully sequenced chloroviruses in public databases. Presented here are the draft genome sequences of 35 additional chloroviruses (287 – 348 Kb/319 – 381 predicted protein encoding genes) collected across the globe; they infect one of three different green algal species. These new data allowed us to analyze the genomic landscape of 41 chloroviruses, which revealed some remarkable features about these viruses. …

Hiv-1 Env C2-V4 Diversification In A Slow-Progressor Infant Reveals A Flat But Rugged Fitness Landscape, S. Abigail Smith, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type-1 (HIV-1) fitness has been associated with virus entry, a process mediated by the envelope glycoprotein (Env). We previously described Env genetic diversification in a Zambian, subtype C infected, slow-progressor child (1157i) in parallel with an evolving neutralizing antibody response. Because of the role the Variable-3 loop (V3) plays in transmission, cell tropism, neutralization sensitivity, and fitness, longitudinally isolated 1157i C2-V4 alleles were cloned into HIV-1_NL4-3-eGFP and -DsRed2 infectious molecular clones. The fluorescent reporters allowed for dual-infection competitions between all patient-derived C2-V4 chimeras to quantify the effect of V3 diversification and selection on fitness. ‘Winners’ …