Genetics and Genomics Commons^™

The Influence Of Environmental Change On Genetic Diversity Across Spatial And Taxonomic Scales, Connor M. French

Dissertations, Theses, and Capstone Projects

The spatial distribution of genetic diversity is of interest to biodiversity scientists and conservationists and is a fundamental metric of biodiversity. Genetic diversity patterns across spatial and taxonomic scales contain information about population and assemblage dynamics that can convey their resilience to environmental change. Ectotherms are especially linked to their environments and may be especially sensitive to fluctuations in the environment over time. Herein, I investigate global and regional patterns of genetic diversity in two groups of ectotherms, insects and lizards, to understand the relationship between environmental change and genetic diversity, from populations to assemblages. Overall, my research aims to …

Complete Genome Sequence Of An Indian Outbreak Strain Of Chikungunya Virus, Eshna Laha, Deepak Jena, Viplov K. Biswas, Sharad Singh, Sunil K. Raghav, Asit K. Pattnaik, Soma Chattopadhyay

Nebraska Center for Virology: Faculty Publications

Here, we report the complete genome sequence of an Indian strain of chikungunya virus isolated from an infected patient from Hyderabad, Andhra Pradesh, India, during a massive outbreak in 2005–2006. The genome length spans 11,811 nucleotides and has a poly(A) tail of 29 residues at the 3′ end.

Diverse Origins Of Near-Identical Antifreeze Proteins In Unrelated Fish Lineages Provide Insights Into Evolutionary Mechanisms Of New Gene Birth And Protein Sequence Convergence, Nathan Rives, Vinita Lamba, C.H. Christina Cheng, Xuan Zhuang

Biological Sciences Faculty Publications and Presentations

Determining the origins of novel genes and the mechanisms driving the emergence of new functions is challenging yet crucial for understanding evolutionary innovations. Recently evolved fish antifreeze proteins (AFPs) offer a unique opportunity to explore these processes, particularly the near-identical type I AFP (AFPI) found in four phylogenetically divergent fish taxa. This study tested the hypothesis of protein sequence convergence beyond functional convergence in three unrelated AFPI-bearing fish lineages. Through comprehensive comparative analyses of newly sequenced genomes of winter flounder and grubby sculpin, along with available high-quality genomes of cunner and 14 other related species, the study revealed that near-identical …

Noise Leads To The Perceived Increase In Evolutionary Rates Over Short Time Scales, Brian C. O'Meara, Jeremy M. Beaulieu

Biological Sciences Faculty Publications and Presentations

Across a variety of biological datasets, from genomes to conservation to the fossil record, evolutionary rates appear to increase toward the present or over short time scales. This has long been seen as an indication of processes operating differently at different time scales, even potentially as an indicator of a need for new theory connecting macroevolution and microevolution. Here we introduce a set of models that assess the relationship between rate and time and demonstrate that these patterns are statistical artifacts of time-independent errors present across ecological and evolutionary datasets, which produce hyperbolic patterns of rates through time. We show …

Psychosocial Outcomes Of Pain And Pain Management In Adults With Osteogenesis Imperfecta: A Qualitative Study, Whitney S Shepherd, Andrew D Wiese, Hannah E Cho, W Conor Rork, M Usman Baig, Kristin M Kostick, Dianne Nguyen, Erin M Carter, Members Of The Bbdc, Chaya N Murali, Marie-Eve Robinson, Sophie C Schneider, Brendan Lee, V Reid Sutton, Eric A Storch

Faculty, Staff and Students Publications

Objectives

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and fractures, short stature, dental abnormalities, hearing loss, scoliosis, and chronic pain. Despite a growing literature on the functional outcomes of OI, limited research has explicitly examined the psychosocial outcomes of pain within OI.

Methods

Adults with OI (N=15) were interviewed to understand pain-related experiences through a thematic analysis of semi-structured interview data. Research team members, genetic research experts, and OI clinicians developed an interview guide focused on topics related to pain and mental health challenges. Participants’ transcripts were coded by two independent coders; codes were then merged …

Hereditary Spherocytosis Due To A Novel Variant, P.Q1034x, In The Beta Subunit Of The Spectrin Gene: A Case Report, Emmalee M. Kugler, Akash Patel, Faraz Afridi, Maria I. Scarano, Rafat Ahmed

Department of Emergency Medicine Faculty Papers

Background: Heterozygous pathogenic variants of SPTB cause hereditary spherocytosis (HS) in a quarter of cases. Case report: A 14-day-old male presenting with persistent anemia and hyperbilirubinemia was diagnosed with HS by increased red blood cell osmotic fragility and decreased fluorescence on the eosin-5′-maleimide binding test. For his failure to thrive and hypotonia, genetic sequencing revealed a de novo variant of the SPTB gene (p.Q1034X) on exon 15. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. A variant of uncertain significance (p.R438W) in the chondroitin sulfate synthase 1 (CHSY1) gene …

How Many Fathers? Frequency Of Multiple Paternity In Soupfin Sharks (Galeorhinus Galeus) From California And Australia, Okoiya Kelly

Theses

Multiple paternity has been widely documented in elasmobranch fishes (sharks, rays, and skates); however, the frequency of multiple paternity (FMP; the percentage of sampled litters having multiple sires) varies greatly both among and within species. Understanding the reasons for this inter- and intraspecific variation in FMP may be key to understanding why females mate with multiple males. The soupfin shark (Galeorhinus galeus) is an understudied species in this regard with only one study previously investigating multiple paternity, in which two out of five litters sampled from New Zealand were found to have multiple sires (FMP = 40.0%). We augmented this …

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …

Whole Genome And Reverse Protein Phase Array Landscapes Of Patient Derived Osteosarcoma Xenograft Models, Chia-Chin Wu, Licai Huang, Zhongting Zhang, Zhenlin Ju, Xingzhi Song, E Anders Kolb, Wendong Zhang, Jonathan Gill, Min Ha, Malcolm A Smith, Peter Houghton, Christopher L Morton, Raushan Kurmasheva, John Maris, Yael Mosse, Yiling Lu, Richard Gorlick, P Andrew Futreal, Hannah C Beird

Faculty, Staff and Student Publications

Osteosarcoma is the most common primary bone malignancy in children and young adults, and it has few treatment options. As a result, there has been little improvement in survival outcomes in the past few decades. The need for models to test novel therapies is especially great in this disease since it is both rare and does not respond to most therapies. To address this, an NCI-funded consortium has characterized and utilized a panel of patient-derived xenograft models of osteosarcoma for drug testing. The exomes, transcriptomes, and copy number landscapes of these models have been presented previously. This study now adds …

Population Genetic Diversity In Two Biological Systems, Alyson Emery

Electronic Theses and Dissertations

Population genetic analysis can be used to answer questions about population structure and composition in many biological systems. Recent improvements to sequencing technologies have made population genetic studies more accessible than ever before. Many of the same techniques can be applied to different biological systems, but some analyses may differ depending on how genetically divergent the populations in question are. Here, we describe two unique projects using next-generation genome sequencing, each looking at population structure at different levels of genetic divergence: the first involved determining interspecific population structure between two species of hybridizing field cricket using a novel sequencing method, …

Akt Disruption Leads To Non-Canonical Apical Constriction In Drosophila Embryos, Vincent Brown

Electronic Theses and Dissertations

The Akt/mTOR pathway (Akt pathway) has largely been examined in terms of its role as the primary nutrient sensing pathway due to its ability to recognize nutrient availability within a cell, particularly amino acids and glucose. Among its nutrient sensing characteristics, this pathway also contributes to a large variety of other cell functions such as cell growth, proliferation, protein synthesis, and cell survival via anti-apoptotic signaling. Although many aspects of this pathway have been carefully studied, the extent to which it regulates embryonic development remains unclear. Here, I examine Akt function in the early Drosophila embryo and demonstrate that Akt …

Technical Note: Assessing Gps Sensor Accuracy Using Real-Time Kinematic Device For Livestock Tracking, Biquan Zhao, Rebecca Mcdermott, Galen E. Erickson, Yijie Xiong

Department of Animal Science: Faculty Publications

The technical aspects of global positioning system (GPS) sensors have been improved substantially over the years, making them valuable and popular tools for livestock tracking. Using GPS sensors allows producers and researchers to locate grazing livestock, monitor their behavior and distribution, and gather referencing information about the health status of the animals and pastures. However, interpreting the behavior of grazing livestock, such as cattle, from GPS data can be difficult due to positioning inaccuracies. Without knowing the positioning accuracy range of GPS sensors, achieving high-level confidence in determining grazing densities and identifying abnormal livestock movement patterns is challenging. …

The Complex Molecular Epileptogenesis Landscape Of Glioblastoma, Victoria Soeung, Ralph B Puchalski, Jeffrey L Noebels

Faculty, Staff and Students Publications

The cortical microenvironment surrounding malignant glioblastoma is a source of depolarizing crosstalk favoring hyperexcitability, tumor expansion, and immune evasion. Neosynaptogenesis, excess glutamate, and altered intrinsic membrane currents contribute to excitability dyshomeostasis, yet only half of the cases develop seizures, suggesting that tumor and host genomics, along with location, rather than mass effect, play a critical role. We analyzed the spatial contours and expression of 358 clinically validated human epilepsy genes in the human glioblastoma transcriptome compared to non-tumor adult and developing cortex datasets. Nearly half, including dosage-sensitive genes whose expression levels are securely linked to monogenic epilepsy, are strikingly enriched …

Forest Defoliation By And Invasive Outbreak Insect: Catastrophic Consequences For A Charismatic Mega Moth, Richard L. Lindroth, Mark R. Zierden, Clay J. Morrow, Patricia C. Fernandez

Aspen Bibliography

Earth is now experiencing declines in insect abundance and diversity unparalleled in human history. The drivers underlying those declines are many, complex, and incompletely known. Here, using a natural experiment, we report the first test of the hypothesis that forest defoliation by an invasive outbreak insect compromises the fitness of a native insect via damage-induced increases in toxicity of the forest canopy. We demonstrate that defoliation by the invasive spongy moth (Lymantria dispar) elicits an average 8.4-fold increase in foliar defense expression among aspen (Populus tremuloides) genotypes. In turn, elevated defense dramatically reduces survivorship, feeding, and …

Simulation Of Crispr-Cas9 Editing On Evolving Barcode And Accuracy Of Lineage Tracing, Fengshuo Liu, Xiang Zhang, Yipeng Yang

Faculty, Staff and Students Publications

We designed a simulation program that mimics the CRISPR-Cas9 editing on evolving barcode and double strand break repair procedure along with cell divisions. Emerging barcode mutations tend to build upon previously existing mutations, occurring sequentially with each generation. This process results in a unique mutation profile in each cell. We sample the barcodes in leaf cells and reconstruct the lineage, comparing it to the original lineage tree to test algorithm accuracy under different parameter settings. Our computational simulations validate the reasonable assumptions deduced from experimental observations, emphasizing that factors such as sampling size, barcode length, multiple barcodes, indel probabilities, and …

Synergistic Activation By Glass And Pointed Promotes Neuronal Identity In The Drosophila Eye Disc, Hongsu Wang, Komal Kumar Bollepogu Raja, Kelvin Yeung, Carolyn A Morrison, Antonia Terrizzano, Alireza Khodadadi-Jamayran, Phoenix Chen, Ashley Jordan, Cornelia Fritsch, Simon G Sprecher, Graeme Mardon, Jessica E Treisman

Faculty, Staff and Students Publications

The integration of extrinsic signaling with cell-intrinsic transcription factors can direct progenitor cells to differentiate into distinct cell fates. In the developing Drosophila eye, differentiation of photoreceptors R1-R7 requires EGFR signaling mediated by the transcription factor Pointed, and our single-cell RNA-Seq analysis shows that the same photoreceptors require the eye-specific transcription factor Glass. We find that ectopic expression of Glass and activation of EGFR signaling synergistically induce neuronal gene expression in the wing disc in a Pointed-dependent manner. Targeted DamID reveals that Glass and Pointed share many binding sites in the genome of developing photoreceptors. Comparison with transcriptomic data shows …

Perspectives On Transition To Adult Healthcare For Adults With Williams Syndrome And Their Caregivers, Andrea Johnson

Theses and Dissertations

Transitioning to adult care services is a crucial time for young adults with a genetic condition. Many of these conditions are diagnosed early in childhood, with follow-up care fragmented and dependent on the specific needs of the individual. Williams syndrome (WS) is a complex genetic condition characterized by multisystemic features. The variation in the clinical presentation of adults with WS can influence the individual’s ability to transition from pediatric care because of its medical complications, variable and poorly characterized psychiatric needs, and intellectual disability that causes difficulty communicating health-related needs to providers. This study focused on understanding the needs of …

Patients’ Experience Of Care Following Perinatal Case Conference, Mary Elise Nolen

Theses and Dissertations

The Perinatal Case Conference (PCC) at Prisma Health-Midlands Maternal-Fetal Medicine (MFM) is a biweekly multidisciplinary meeting to discuss pregnancies with prenatally identified congenital anomalies. Patients are primarily cared for by MFM and may have appointments with various subspecialists during their pregnancy. The goals of the PCC are multidisciplinary collaboration in planning for the management of each pregnancy and familiarizing each practitioner with the pending cases, so if or when intervention is needed, the clinicians are familiar with the case.

Researchers performed a chart review and surveyed patients whose pregnancies were discussed in the PCC to learn the patient’s perspective of …

Perception Of Alzheimer’S Actionability Among End Users Of Direct-To-Consumer Genetic Tests, Emily Mason

Theses and Dissertations

The APOE ε4 allele is the best-known genetic risk factor for developing late-onset Alzheimer’s disease. Although new evidence is emerging, the extent to which lifestyle improvements can reduce Alzheimer’s risk needs further investigation. Research suggests that individuals with a higher genetic risk may be more likely to engage in risk-reducing health behavior changes following results disclosure. This study aimed to better understand these findings by assessing the health behavior and perceptions of Alzheimer’s actionability among consumers of DTC genetic tests. Our study revealed that individuals with 2 copies of the APOE ε4 allele were less likely to make lifestyle modifications …

Assessing Obgyn Residents’ Knowledge, Attitudes, And Current Practices For Carrier Screening, Aubrey Morgan Surian

Theses and Dissertations

Obstetricians and gynecologists (OBGYNs) are the main providers that order carrier screening on a regular basis, so it is important to understand their knowledge, attitudes, and current practices regarding this screening. There are two primary professional organizations that have established practice guidelines for carrier screening, the American College of Obstetrics and Gynecology (ACOG) and American College of Medical Genetics (ACMG). With the growth of pan-ethnic carrier screening, these guidelines have become remarkably different. This study aimed to assess resident OBGYN’s utilization of pan-ethnic carrier screening, discern any discrepancies between knowledge, attitudes, and current practices, identify possible practice resources that may …