Genetics and Genomics Commons^™

Barriers To Expansion Of Supervision Networks At Genetic Counseling Training Programs, Jordan E. Berg

Dissertations and Theses (Open Access)

Job openings outpace new graduates due to exponential growth in genetic counseling, leading to a workforce shortage. Expanding training slots to meet this demand presumably is linked to the number of supervisors. Thus, there is a need to systematically review barriers to supervision. This study aimed to determine and compare barriers to expansion of supervision networks at genetic counseling training programs as perceived by current supervisors, non-supervisors, and Program Directors. Certified genetic counselors were recruited via National Society of Genetic Counselors e-blast with an invitation to complete an online survey; Program Directors were emailed personal letters of invitation. Twenty-three Program …

Targeted Germ Cell Knockdown Of Xlr3 In Mus Musculus, Caity Miller

Honors Scholar Theses

The X chromosome is rather distinct from autosomes due to the unique regulatory and functional characteristics it exhibits. Xlr3 is just one gene in a superfamily of highly related, and homologous genes found on the X chromosome in mice. Xlr3 is part of a complex, imprinted locus, of which the function is not well understood, although its protein product can be found in testis and oocyte. However, it is theorized that the region may be implicated in the progression of meiosis, due to localization of XLR3. This study sought to characterize the function of Xlr3 through the use of a …

Study Of Rickettsia Parkeri Colonization And Proliferation In The Tick Host Amblyomma Maculatum (Acari: Ixodidae), Khemraj Budachetri

Dissertations

Amblyomma maculatum (Gulf coast tick) ticks are prevalent across the Atlantic to Gulf Coast region of United States. These ticks are recognized vectors of Rickettsia parkeri, a spotted fever group of Rickettsia (SFGR) known to cause American boutonneuse fever associated with fever and eschar rashes localized to the site of bites. We hypothesized that Rickettsia parkeri colonization and proliferation in the tick vector involve pathogen-symbiont dynamics and tick-pathogen interactions, which influence rickettsial transmission to the victims after tick bites. The rickettsial infection is maintained across the tick life cycle for many generations due to transovarial and transstadial transmission of …

A Leishmania Secretion System For The Expression Of Major Ampullate Spidroin Mimics, Todd A. Lyda, Elizabeth L. Wagner, Andre X. Bourg, Congyue Peng, Golnaz Najaf Tomaraei, Delphine Dean, Marian S. Kennedy, William R. Marcotte Jr.

Publications

Spider major ampullate silk fibers have been shown to display a unique combination of relatively high fracture strength and toughness compared to other fibers and show potential for tissue engineering scaffolds. While it is not possible to mass produce native spider silks, the potential ability to produce fibers from recombinant spider silk fibers could allow for an increased innovation rate within tissue engineering and regenerative medicine. In this pilot study, we improved upon a prior fabrication route by both changing the expression host and additives to the fiber pulling precursor solution to improve the performance of fibers. The new expression …

Denoising Tandem Mass Spectrometry Data, Felix Offei

Electronic Theses and Dissertations

Protein identification using tandem mass spectrometry (MS/MS) has proven to be an effective way to identify proteins in a biological sample. An observed spectrum is constructed from the data produced by the tandem mass spectrometer. A protein can be identified if the observed spectrum aligns with the theoretical spectrum. However, data generated by the tandem mass spectrometer are affected by errors thus making protein identification challenging in the field of proteomics. Some of these errors include wrong calibration of the instrument, instrument distortion and noise. In this thesis, we present a pre-processing method, which focuses on the removal of noisy …

Statistical Methods For Two Problems In Cancer Research: Analysis Of Rna-Seq Data From Archival Samples And Characterization Of Onset Of Multiple Primary Cancers, Jialu Li

Dissertations and Theses (Open Access)

My dissertation is focused on quantitative methodology development and application for two important topics in translational and clinical cancer research.

The first topic was motivated by the challenge of applying transcriptome sequencing (RNA-seq) to formalin-fixation and paraffin-embedding (FFPE) tumor samples for reliable diagnostic development. We designed a biospecimen study to directly compare gene expression results from different protocols to prepare libraries for RNA-seq from human breast cancer tissues, with randomization to fresh-frozen (FF) or FFPE conditions. To comprehensively evaluate the FFPE RNA-seq data quality for expression profiling, we developed multiple computational methods for assessment, such as the uniformity and continuity …

Proteomic Identification Of Histone Post-Translational Modifications Induced By Dna Double-Strand Breaks And Novel Proteins Involved In The Dna Damage Response, Pingping Wang

Dissertations and Theses (Open Access)

Inaccurate repair of DNA double-strand breaks (DSBs) can lead to DNA mutation and chromosome rearrangements, causing human diseases such as cancer. Although we know the basic mechanisms of DSB repair, the added complexities in the chromatin context are unclear. This is partially due to the lack of unbiased systems for identifying proteins and post-translational modifications (PTMs) involved in DSB repair. In this work, we established a novel method, termed DSB-ChAP-MS (Double Strand Break-Chromatin Affinity Purification with Mass Spectrometry), for the affinity purification of a sequence-specific single copy endogenous chromosomal locus containing a DSB, followed by the proteomic identification of enriched …

Non-Coding Rnas Identify The Intrinsic Molecular Subtypes Of Muscle-Invasive Bladder Cancer, Andrea E. Ochoa

Dissertations and Theses (Open Access)

NON-CODING RNAS IDENTIFY THE INTRINSIC MOLECULAR SUBTYPES OF MUSCLE-INVASIVE BLADDER CANCER

Andrea Elizabeth Ochoa, B.S.

Advisory Professors: David J. McConkey, Ph.D. and Joya Chandra, Ph.D.

There has been a recent explosion of genomics data in muscle-invasive bladder cancer (MIBC) to better understand the underlying biology of the disease that leads to the high amount of heterogeneity that is seen clinically. These studies have identified relatively stable intrinsic molecular subtypes of MIBC that show similarities to the basal and luminal subtypes of breast cancer. However, previous studies have primarily focused on protein-coding genes or DNA mutations/alterations.

There is emerging evidence implicating …

Attitudes To Ward And Uptake Of Prenatal Genetic Screening And Testing In Twin Pregnancies, Kathryn M. Reese

Dissertations and Theses (Open Access)

The rate of twinning is rising and is associated with delayed age at childbirth and increased infertility treatments. Since the introduction of non-invasive prenatal testing, interest in and uptake of genetic screening and testing in twin pregnancies has not been investigated. Therefore, this study aimed to describe the attitudes toward and uptake of current prenatal genetic screening and testing options in twin pregnancies. Forty-two women with twin gestations were recruited from UTHealth and Baylor College of Medicine sites between August 2016 and January 2017 for participation in a descriptive study consisting of a questionnaire (n=42) and semi-structured phone interview (n=15). …

The Utilization Of Prenatal Microarray: A Survey Of Current Genetic Counseling Practices And Barriers, Leslie N. Durham, Leslie Durham

Dissertations and Theses (Open Access)

Chromosomal microarray (CMA) assesses chromosome copy number variants (CNVs) missed by standard karyotyping. The American College of Obstetricians and Gynecologists (ACOG) recommends CMA for all patients with fetuses with an ultrasound anomaly and suggests that it be made available to all women undergoing invasive testing. In order to assess prenatal genetic counselors’ (GCs) practices regarding the utilization of CMA we conducted a survey of their current practices, attitudes, and perceived barriers. Of the 192 respondents, 183 (95%) have incorporated CMA into clinical practice with the majority (64%) believing that the benefits of CMA outweigh the harms. However, only half (52%) …

Undergraduate Student Perceptions And Awareness Of Genetic Counseling, Amanda Gerard

Dissertations and Theses (Open Access)

Genetic counseling (GC) is a rapidly expanding field, and the supply of certified genetic counselors is currently unable to keep up with job demand. Research is fairly limited regarding the awareness and perceptions potential genetic counseling program applicants have of the field and what factors most influence their interest in the field. This study aimed to examine some of these topics. The current study includes data collected from 1,389 undergraduate students in the sciences at 23 universities across the United States who were surveyed regarding information related to their awareness, perceptions, knowledge, and interest in GC. Data analysis was performed …

Attitudes Of Clinicians To Wards Cardiac Surgery And Trisomy 18, Meagan Kaulfus

Dissertations and Theses (Open Access)

Trisomy 18 is an autosomal trisomy characterized by minor to major birth defects, severe disabilities, and high rates of pre- and neonatal mortality. Interventions for these infants have traditionally been withheld with focus instead on palliative support. The issues and attitudes surrounding surgical treatment of congenital heart defects, which occur in approximately 90% of infants with trisomy 18, is of our study’s interest as recent literature has indicated that cardiac surgery is being performed and may lead to improved survival compared to palliative care. In this study, the attitudes of clinicians of multiple specialties towards cardiac surgery for infants with …

Analysis Of The Biochemical And Cellular Activities Of Substrate Binding By The Molecular Chaperone Hsp110/Sse1, Veronica M. Garcia

Dissertations and Theses (Open Access)

Molecular chaperones ensure protein quality during protein synthesis, delivery, damage repair, and degradation. The ubiquitous and highly conserved molecular chaperone 70-kDa heat-shock proteins (Hsp70s) are essential in maintaining protein homeostasis by cycling through high and low affinity binding of unfolded protein clients to facilitate folding. The Hsp110 class of chaperones are divergent relatives of Hsp70 that are extremely effective in preventing protein aggregation but lack the hallmark folding activity seen in Hsp70s. Hsp110s serve as Hsp70 nucleotide exchange factors (NEF) that facilitate the Hsp70 folding cycle by inducing release of protein substrate from Hsp70, thus recycling the chaperone for a …

Understanding The Mechanism Of Genomic Instability During Replicative Aging In Budding Yeast, Sangita Pal

Dissertations and Theses (Open Access)

Aging brings a gradual decline in molecular fidelity and biological functionality, resulting in age related phenotypes and diseases. Despite continued efforts to uncover the conserved aging pathways among eukaryotes, exact molecular causes of aging are still poorly understood. One of the most important hallmarks of aging is increased genomic instability. However, there remains much ambiguity as to the cause. I am studying the replicative life span (RLS) of the genetically tractable model organism Saccharomyces cerevisiae, or budding yeast using the innovative “mother enrichment program” as the method to isolate unparalleled numbers of aged yeast cells to investigate the molecular changes …

A Genetic Analysis Of Nuclear Functions Of The Lipin Protein In Drosophila Melanogaster, Xeniya Rudolf

Graduate Theses and Dissertations

Lipins are a family of proteins that have critical functions in the control of fat storage and energy homeostasis. Biochemically, lipins have two functions. They provide an enzymatic activity (phosphatidate phosphatase or PAP activity) in the glycerol-3 phosphate pathway that leads to the production of storage fats (triacylglycerols). In addition, they play a role in the regulation of genes in the cell nucleus as transcriptional co-regulators. The PAP activity of lipins has been widely studied in a number of organisms. However, the transcriptional co-regulator function is not as well described in the literature. The transcriptional function of lipins depends on …

Genetic Polymorphisms Of The Glucocorticoid Receptor And Interleukin-8 Receptor Genes Are Related To Production Traits And Hair Coat Score In Crossbred Cattle, Avery Deaton

Animal Science Undergraduate Honors Theses

The objective of this thesis was to identify polymorphisms in the glucocorticoid receptor (GR) and interleukin-8 receptor (CXCR2) genes and to associate genotypes between the above mentioned polymorphisms and production traits in crossbred cattle. The hypothesis was that polymorphisms will exist for GR and CXCR2 genes and will be linked to production traits. Glucocorticoid receptors have been positively associated with higher milk yields, lactose content, feed intake, and feed conversion rates. Interleukin-8 genes are part of the innate immune response and help with many aspects of female reproduction health, such as protecting the embryo from the maternal immune system during …

Science, Between The Lines: Rosalind Franklin, Rachael Renzi

Senior Honors Projects

The purpose of this paper is to contrast scientific rhetoric with creative biographical writing style. Both forms of communication rely on specific syntax and styles to describe research findings to the appropriate audiences, but the often passive format of scientific literature excludes the passionate reasonings of the researcher. In order to understand why the scientist is kept separate from his or her published findings, I am going to experiment with the two contrasting forms. Throughout the paper, each form will be tested and used at varying levels. Both scientific and creative writing will be mixed. To emphasize the technically dense …

The Effect Of Galactose On The Expression Of Genes Regulated By Rrp6p, Mary Megan Pelkowski, Kevin Callahan

The Review: A Journal of Undergraduate Student Research

Gene expression is a multi-faceted phenomenon, governed not only by the sequence of nucleotides, but also by the extent to which a particular gene gets transcribed, how the transcript is processed, and whether or not the transcript ever makes it out of the nucleus. Rrp6p is a 5’-3’ exonuclease that can function independently and as part of the nuclear exosome in Saccharomyces cerevisiae (Portin, 2014). It degrades various types of aberrant RNA species including small nuclear RNAs, small nucleolar RNAs, telomerase RNA, unspliced RNAs, and RNAs that have not been properly packaged for export (Butler & Mitchell, 2010). This exosome …

Sickle Cell Anemia: Current Treatments And Potential Advancements, Vanessa Martinez

Selected Honors Theses

Sickle cell anemia is a disease that affects red blood cells, specifically the hemoglobin protein. An amino acid mutation in the gene that encodes β-globin leads to malformation of the β subunit of hemoglobin.3, Valine becomes glutamic acid in the mutated β-globin gene.9 The mutation malformation leads to the red blood cells becoming sickle shaped, or crescent shaped.3,4 The sickle shape of red blood cells in individuals with sickle cell disease leads to vaso-occlusive crisis.9 Vaso-occlusive crisis includes complications such as blood clotting, chronic pain, organ failure, organ death, and possibly early mortality.9 The Centers for Disease Control and Prevention …

Systematic Analysis Of Whole Exome Sequencing Determines Ret G691s Polymorphism As Germline Variant In Melanoma, Brent J. Smith Jr, Jennifer D. Hintzsche, Carol M. Amato, Aik-Choon Tan, Keith R. Wells, Allison J. Applegate, Rita T. Gonzalez, Jodie R. Barr, William A. Robinson

Marshall Journal of Medicine

Abstract

The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by glial cell derived neutrotrophic factor (GDNF). Previous studies have found that a single nucleotide polymorphism (SNP), RETp (G691S), in the juxtamembrane domain enhances the signaling pathway and promotes tumor growth by GDNF in pancreatic and thyroid cancer in addition to melanoma. It is uncertain however whether this SNP is a germline variant or somatic mutation. A prior study reported that the RETp variant was a germline SNP in desmoplastic and non-desmoplastic melanomas. In the present study, we examined both melanoma tissue samples and matching peripheral blood DNA …

A Longitudinal Cline Characterizes The Genetic Structure Of Human Populations In The Tibetan Plateau, Choongwon Jeong, Benjamin M. Peter, Buddha Basnyat, Maniraj Neupane, Geoff Childs, Sienna Craig, John Novembre, Anna Di Rienzo

Dartmouth Scholarship

Indigenous populations of the Tibetan plateau have attracted much attention for their good performance at extreme high altitude. Most genetic studies of Tibetan adaptations have used genetic variation data at the genome scale, while genetic inferences about their de- mography and population structure are largely based on uniparental markers. To provide genome-wide information on population structure, we analyzed new and published data of 338 individuals from indigenous populations across the plateau in conjunction with world- wide genetic variation data. We found a clear signal of genetic stratification across the east- west axis within Tibetan samples. Samples from more eastern locations …

Genome-Wide Analysis Of Atp-Binding Cassette (Abc) Transporters In The Sweetpotato Whitefly, Bemisia Tabaci, Lixia Tian, Tianxue Song, Rongjun He, Yang Zeng, Wen Xie, Qingjun Wu, Shaoli Wang, Xuguo Zhou, Youjun Zhang

Entomology Faculty Publications

Background: ABC transporter superfamily is one of the largest and ubiquitous groups of proteins. Because of their role in detoxification, insect ABC transporters have gained more attention in recent years. In this study, we annotated ABC transporters from a newly sequenced sweetpotato whitefly genome. Bemisia tabaci Q biotype is an emerging global invasive species that has caused extensive damages to field crops as well as ornamental plants.

Results: A total of 55 ABC transporters containing all eight described subfamilies (A to H) were identified in the B. tabaci Q genome, including 8 ABCAs, 3 ABCBs, 6 ABCCs, 2 ABCDs, 1 …

Accumulation And Expression Of Multiple Antibiotic Resistance Genes In Arcobacter Cryaerophilus That Thrives In Sewage, Jess A. Millar, Rahul Raghavan

Biology Faculty Publications and Presentations

We explored the bacterial diversity of untreated sewage influent samples of a wastewater treatment plant in Tucson, AZ and discovered that Arcobacter cryaerophilus, an emerging human pathogen of animal origin, was the most dominant bacterium. The other highly prevalent bacteria were members of the phyla Bacteroidetes and Firmicutes, which are major constituents of human gut microbiome, indicating that bacteria of human and animal origin intermingle in sewage. By assembling a near-complete genome of A. cryaerophilus, we show that the bacterium has accumulated a large number of antibiotic resistance genes (ARGs) probably enabling it to thrive in the wastewater. We also …

Discovery And Fine-Mapping Of Adiposity Loci Using High Density Imputation Of Genome-Wide Association Studies In Individuals Of African Ancestry: African Ancestry Anthropometry Genetics Consortium, Maggie C. Y. Ng, Mariaelisa Graff, Yingchang Lu, Anne E. Justice, Poorva Mudgal, Ching-Ti Liu, Kristin Young, Lisa R. Yanek, Mary F. Feitosa, Mary K. Wojczynski, Kristin Rand, Jennifer A. Brody, Brian E. Cade, Latchezar Dimitrov, Qing Duan, Xiuqing Guo, Leslie A. Lange, Michael A. Nalls, Hayrettin Okut, Salman M. Tajuddin, Bamidele O. Tayo, Sailaja Vedantam, Jonathan P. Bradfield, Guanjie Chen, Wei-Min Chen, Alessandra Chesi, Marguerite R. Irvin, Badri Padhukasahasram, Jennifer A. Smith, Wei Zheng, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Genome-wide association studies (GWAS) have identified > 300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHR_adjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHR_adjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified …

Molecular And Biochemical Technologies For Modifying Plant Cell Walls And Producing Functional Biobased Products, Ningning Zhang

Student Theses and Dissertations

There is a continuing need for new molecular and biochemical processing technologies to more sustainably utilize biomass such as sugar beet pulp for environmental and economic benefit. This research project addressed the overarching research hypothesis that innovative molecular and biochemical technologies can enable more efficient processing of plant biomass and generate renewable biobased products for food and industrial use. Specifically, this research investigated upstream processing technologies toward re-engineering the plant cell wall for improved biomass processability and downstream processing technologies for efficient cell wall-depolymerizing (CWD) enzyme production and biomass processing. There were two Specific Aims addressed in this project: 1.) …

Draft Nuclear Genome Sequence Of The Liquid Hydrocarbon–Accumulating Green Microalga Botryococcus Braunii Race B (Showa), Daniel R. Browne, Jerry Jenkins, Jeremy Schmutz, Shengqiang Shu, Kerrie Barry, Jane Grimwood, Jennifer Chiniquy, Aditi Sharma, Thomas Daniel Niehaus, Taylor L. Weiss, Andrew T. Koppisch, David T. Fox, Suraj Dhungana, Shigeru Okada, Joe Chappell, Timothy P. Devarenne

Plant and Soil Sciences Faculty Publications

Botryococcus braunii has long been known as a prodigious producer of liquid hydrocarbon oils that can be converted into combustion engine fuels. This draft genome for the B race of B. braunii will allow researchers to unravel important hydrocarbon biosynthetic pathways and identify possible regulatory networks controlling this unusual metabolism.

Rseqrep: Rna-Seq Reports, An Open-Source Cloud-Enabled Framework For Reproducible Rna-Seq Data Processing, Analysis, And Result Reporting, Travis L. Jensen, Michael Frasketi, Kevin Conway, Leigh Villarroel, Heather Hill, Konstantinos Krampis, Johannes B. Goll

Publications and Research

RNA-Seq is increasingly being used to measure human RNA expression on a genome-wide scale. Expression profiles can be interrogated to identify and functionally characterize treatment-responsive genes. Ultimately, such controlled studies promise to reveal insights into molecular mechanisms of treatment effects, identify biomarkers, and realize personalized medicine. RNA-Seq Reports (RSEQREP) is a new open-source cloud-enabled framework that allows users to execute start-to-end gene-level RNA-Seq analysis on a preconfigured RSEQREP Amazon Virtual Machine Image (AMI) hosted by AWS or on their own Ubuntu Linux machine. The framework works with unstranded, stranded, and paired-end sequence FASTQ files stored locally, on Amazon Simple Storage …

Longitudinal Peripheral Blood Transcriptional Analysis Of A Patient With Severe Ebola Virus Disease., John C Kash, Kathie-Anne Walters, Jason Kindrachuk, David Baxter, Kelsey Scherler, Krisztina B Janosko, Rick D Adams, Andrew S Herbert, Rebekah M James, Spencer W Stonier, Matthew J Memoli, John M Dye, Richard T Davey, Daniel S Chertow, Jeffery K Taubenberger

Articles, Abstracts, and Reports

The 2013-2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U.S. Food and Drug Administration-approved vaccines or therapies. We report a detailed study of host gene expression as measured by microarray in daily …

Lysine Residues Of Interferon Regulatory Factor 7 Affect The Replication And Transcription Activatormediated Lytic Replication Of Kaposi’S Sarcomaassociated Herpesvirus/Human Herpesvirus 8, Tianzheng Zhang, Ying Wang, Li Zhang, Bin Liu, Jinhui Xie, Charles Wood, Jinzhong Wang

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) infection goes through latent and lytic phases, which are controlled by the viral replication and transcription activator (RTA). Upon KSHV infection, the host responds by suppressing RTA-activated lytic gene expression through interferon regulatory factor 7 (IRF-7), a key regulator of host innate immune response. Lysine residues are potential sites for post-translational modification of IRF-7, and were suggested to be critical for its activity. In this study, we analysed the 15 lysine residues for their effects on IRF-7 function by site-directed mutagenesis. We found that some mutations affect the ability of IRF-7 to activate interferon (IFN)-a1 and …

Development Of Site Fidelity In The Nocturnal Amblypygid, Phrynus Marginemaculatus, Jacob M. Graving, Verner P. Bingman, Eileen Hebets, Daniel D. Wiegmann

Eileen Hebets Publications

Amblypygids are capable of navigation in the complex terrain of rainforests in near complete darkness. Path integration is unnecessary for successful homing, and the alternative mechanisms by which they navigate have yet to be elucidated. Here, our aims were to determine whether the amblypygid Phrynus marginemaculatus could be trained to reliably return to a target shelter in a laboratory arena—indicating goal recognition—and to document changes in behavior associated with the development of fidelity. We recorded nocturnal movements and space use by individuals over five nights in an arena in which subjects were provided with two shelters that differed in quality. …