Genetics and Genomics Commons^™

Characterization Of Putative Wnt3a-Inducible Enhancers, Katelynn C. Lee, Nicholas Hum, Aimy Sebastian, Gabriela Loots

STAR Program Research Presentations

The Wnt signaling pathway has been previously shown to play a major role in regulating bone metabolism and it is emerging as a target for the therapeutic intervention of bone thinning disorders such as osteoporosis. Several Wnt proteins have been shown to be expressed in bone and mutations in Wnt pathway members such as Wnt co-receptor Lrp5 and Wnt inhibitor Sost have been shown to be associated with low or high bone mass disorders, however, very little is known about specific roles played by different Wnt ligands in bone development, repair and remodeling. To identify downstream targets of Wnt signaling …

Hippocalcin Response To Calcium: Do Conserved Tryptophans – W30 Or W103 – Matter?, Sunkesula K. Sagar

Graduate School of Biomedical Sciences Theses and Dissertations

Changes in intracellular calcium levels play a very important role in cell signaling, in turn, affecting neuronal functions such as memory, learning and cell death. A class of proteins called Neuronal Calcium Sensor (NCS) proteins serves to modulate the functioning of the neuronal cells in response to changes in calcium levels, and prevent neuronal apoptosis. Structurally, all NCS proteins have 4 calcium-binding EF hand motifs, although EF1 does not bind to calcium in many members. All NCS proteins have an acyl modification at the N- terminus – where a myristoyl group is added post-translationally. Hippocalcin (HPCA) is an NCS protein, …

Conformational Dynamics Of Dnaa Protein Of Bacillus Anthracis In The Initiation Of Dna Replication: A Fluorescence Resonance Energy Transfer Study, Meera J. Patel

Graduate School of Biomedical Sciences Theses and Dissertations

A precursor of the origin recognition complex proteins in eukaryotes, the DnaA protein, a single-subunit protein found in all prokaryotes, p1ays a significant role in the initiation of DNA replication. The DnaA protein in Gram-negative Escherichia coli (DnaA_EC) identifies, binds and activates specific DNA sequences at the origin of replication, oriC, initiating the duplication of the prokaryotic genome. Using DnaA_EC as a guide, we selected the full-length form of DnaA from Gram-positive Bacillus anthracis (DnaA_BA) as our model for studying. We have cloned, mutated, expressed and purified large quantities of DnaA_BA protein due to …

A Parallel Algorithm For Compression Of Big Next-Generation Sequencing Datasets, Sandino N. Vargas Perez, Fahad Saeed

Parallel Computing and Data Science Lab Technical Reports

With the advent of high-throughput next-generation sequencing (NGS) techniques, the amount of data being generated represents challenges including storage, analysis and transport of huge datasets. One solution to storage and transmission of data is compression using specialized compression algorithms. However, these specialized algorithms suffer from poor scalability with increasing size of the datasets and best available solutions can take hours to compress gigabytes of data. In this paper we introduce paraDSRC, a parallel implementation of DSRC algorithm using a message passing model that presents reduction of the compression time complexity by a factor of O(1/p ). Our experimental results show …

Bioregulatory Systems Medicine: An Innovative Approach To Integrating The Science Of Molecular Networks, Inflammation, And Systems Biology With The Patient's Autoregulatory Capacity?, Alyssa W Goldman, Yvonne Burmeister, Konstantin Cesnulevicius, Martha Herbert, Mary Kane, David Lescheid, Timothy Mccaffrey, Myron Schultz, Bernd Seilheimer, Alta Smit, Georges St Laurent, Brian Berman

Medicine Faculty Publications

Bioregulatory systems medicine (BrSM) is a paradigm that aims to advance current medical practices. The basic scientific and clinical tenets of this approach embrace an interconnected picture of human health, supported largely by recent advances in systems biology and genomics, and focus on the implications of multi-scale interconnectivity for improving therapeutic approaches to disease. This article introduces the formal incorporation of these scientific and clinical elements into a cohesive theoretical model of the BrSM approach. The authors review this integrated body of knowledge and discuss how the emergent conceptual model offers the medical field a new avenue for extending the …

A Dual Function Of White Coloration In A Nocturnal Spider Dolomedes Raptor (Araneae: Pisauridae), Tai-Shen Lin, Shichang Zhang, Chen-Pan Liao, Eileen A. Hebets, I-Min Tso

Eileen Hebets Publications

Nocturnal animals frequently possess seemingly conspicuous color patterns that can function in a variety of ways (e.g. prey attraction, camouflage, predator avoidance, etc.). The use of color patterns in intraspecific signaling, especially reproductive activities, in nocturnal animals has received relatively little attention. This study tested for a dual function of color in the nocturnal fishing spider, Dolomedes raptor (Araneae: Pisauridae), whose males develop dimorphic white stripes at sexual maturation. We tested for a role in foraging as well as mate assessment. First, quantifications of the natural variation of male stripes indicated a correlation between stripe area and male body size …

Evaluation Of Reduced Subsets Of Single Nucleotide Polymorphisms For The Prediction Of Age At Puberty In Sows, Katherine L. Lucot, Matthew L. Spangler, Melanie D. Trenhaile, Stephen D. Kachman, Daniel C. Ciobanu

Department of Animal Science: Faculty Publications

Genomic information could be used efficiently to improve traits that are expensive to measure, sex limited or expressed late in life. This study analyzed the phenotypic variation explained by major SNPs and windows for age at puberty in gilts, an indicator of reproductive longevity. A genome-wide association study using 56,424 SNPs explained 25.2% of the phenotypic variation in age at puberty in a training set (n = 820). All SNPs from the top 10% of 1-Mb windows explained 33.5% of the phenotypic variance compared to 47.1% explained by the most informative markers (n = 261). In an evaluation population, consisting …

Intracellular Listeria Monocytogenes Comprises A Minimal But Vital Fraction Of The Intestinal Burden Following Foodborne Infection, Grant S. Jones, Kate M. Bussell, Tanya Myers-Morales, Abigail M. Fieldhouse, Elsa N. Bou Ghanem, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Listeria monocytogenes is a highly adaptive bacterium that replicates as a free-living saprophyte in the environment as well as a facultative intracellular pathogen that causes invasive foodborne infections. The intracellular life cycle of L. monocytogenes is considered to be its primary virulence determinant during mammalian infection; however, the proportion of L. monocytogenes that is intracellular in vivo has not been studied extensively. In this report, we demonstrate that the majority of wild-type (strain EGDe) and mouse-adapted (InlA^m-expressing) L. monocytogenes recovered from the mesenteric lymph nodes (MLN) was extracellular within the first few days after foodborne infection. In addition, …

Beyond Bivariate Correlations: Three-Block Partial Least Squares Illustrated With Vegetation, Soil, And Topography, Daehyun Kim, Thomas J. Dewitt, César S. B. Costa, John A. Kupfer, Ryan W. Mcewan, J. Anthony Stallins

Biology Faculty Publications

Ecologists, particularly those engaged in biogeomorphic studies, often seek to connect data from three or more domains. Using three-block partial least squares regression, we present a procedure to quantify and define bi-variance and tri-variance of data blocks related to plant communities, their soil parameters, and topography. Bi-variance indicates the total amount of covariation between these three domains taken in pairs, whereas tri-variance refers to the common variance shared by all domains. We characterized relationships among three domains (plant communities, soil properties, topography) for a salt marsh, four coastal dunes, and two temperate forests spanning several regions in the world. We …

Distinct Physiological Roles For The Two Isoforms Of The Er Chaperone Grp170 In Caenorhabditis Elegans, Yuanyuan Li

Biology Theses

GRP170 is a large molecular chaperone found in the ER of all eukaryotes. The nematode Caenorhabditis elegans has two loci encoding GRP170: T24H7.2 (grp170a) and T14G8.3 (grp170b). The phenotypes of nematodes genetically deficient for either grp170a or grp170b were compared to a standard laboratory strain with functional grp170 loci. Worms that were deficient for grp170a developed 32% slower than the control strain. The loss of grp170a had a significant but modest reduction on the life span compared to the control strain. Worms deficient for grp170a also displayed significantly increased embryonic lethality and resulted in 6.9% arrested embryos. The loss of …

Differential Regulation Of The Two Grp170 Paralogues Of Caenorhabditis Elegans, Antonio L. Rockwell

Biology Theses

Abstract of a Thesis

Differential Regulation of the Two grp170 Paralogues of Caenorhabditis elegans

Caenorhabditis elegans has two loci encoding the large eukaryotic molecular chaperone Grp170, grp170a (T24H7.2) and grp170b (T14G8.3). To investigate expression of the two C. elegans grp170 loci during ER stress, the Unfolded Protein Response (UPR) was induced with the glycosylation inhibitor tunicamycin. Levels of grp170a mRNA did not significantly change in response to tunicamycin treatment while the levels of grp170b mRNA increased 6-fold. ER stress induction of grp170b was unaffected in worms defective for the ATF6 and PERK-1 UPR signal transduction pathways. However, worms defective …

An Analysis Of The Differential Methylation And Expression Of Imprinted Genes In M. M. Musculus, M. M. Domesticus, And Their Hybrids, Anna P. Rice

All NMU Master's Theses

Epigenetics has been found to have an effect on many aspects of biology. Epigenetics refers to modifications of the double-stranded DNA molecule, which do not change the nucleotide sequence but do affect gene expression. DNA methylation is a type of epigenetic modification. Genomic imprinting is a pattern of gene expression that is primarily achieved through DNA methylation, and it results in the expression of only one allele at a particular locus. In this study, I analyzed the methylation patterns of five imprinted genes in the hybrids of two different lab strains of the house mouse subspecies, M. m. musculus and …

A Search For Parent-Of-Origin Effects On Honey Bee Gene Expression, Sarah D. Kocher, Jennifer M. Tsuruda, Joshua D. Gibson, Christine M. Emore, Miguel E. Arechavaleta-Velasco, David C. Queller, Joan E. Strassmann, Christina M. Grozinger, Michael R. Gribskov, Phillip San Miguel, Rick Westerman, Greg J. Hunt

Biology Faculty Research

Parent-specific gene expression (PSGE) is little known outside of mammals and plants. PSGE occurs when the expression level of a gene depends on whether an allele was inherited from the mother or the father. Kin selection theory predicts that there should be extensive PSGE in social insects because social insect parents can gain inclusive fitness benefits by silencing parental alleles in female offspring. We searched for evidence of PSGE in honey bees using transcriptomes from reciprocal crosses between European and Africanized strains. We found 46 transcripts with significant parent-of-origin effects on gene expression, many of which overexpressed the maternal allele. …

Identification Of Familial Wilms Tumor Predisposition Genes Using Whole Genome Sequencing, Timothy B. Palculict

Dissertations and Theses (Open Access)

Wilms tumor, a childhood tumor arising from undifferentiated renal mesenchyme, is diagnosed in North America at a frequency of 1 in 10,000 live births and accounts for 5% of all pediatric cancers. The etiology of Wilms tumor is heterogeneous with multiple genes known to have an effect on Wilms tumor development; however, these genes are rarely associated with familial Wilms tumor. Gene mutations in WT1, WTX, CTNNB1 and TP53 are observed in a third of sporadic tumors, while the causative gene(s) responsible for familial Wilms tumor are largely unknown. Approximately 2% of Wilms tumor patients have a family …

In Vivo Significance Of The Mdm4 And P73 Interaction During Development And Tumorigenesis, Mehrnoosh Tashakori

Dissertations and Theses (Open Access)

The tumor suppressor protein p53 is negatively regulated by Mdm4 protein. The significance of such regulation was determined from mouse models. Mdm4-deficient mice are embryonic lethal at E7.5 in a p53-dependent manner. p73, a member of the p53-family, is a transcription factor with tumor suppressor activity. In vitro studies show that Mdm4 binds to p73 and, further, comprehensive biochemical studies revealed that Mdm4 has higher affinity for p73 than p53. However, little is known about the significance of the Mdm4 and p73 interaction in vivo. This study aimed to elucidate the biological consequences of this interaction during embryogenesis …

Germline Mutation Detection In Next Generation Sequencing Data And Tp53 Mutation Carrier Probability Estimation For Li-Fraumeni Syndrome, Gang Peng

Dissertations and Theses (Open Access)

Next generation sequencing technology has been widely used in genomic analysis, but its application has been compromised by the missing true variants, especially when these variants are rare. We proposed a family-based variant calling method, FamSeq, integrating Mendelian transmission information with de novo mutation and sequencing data to improve the variant calling accuracy. We investigated the factors impacting the improvement of family-based variant calling in simulation data and validated it in real sequencing data. In both simulation and real data, FamSeq works better than the single individual based method.

In FamSeq, we implemented four different methods for the Mendelian genetic …

Detection Of Genes Influencing Chronic And Mendelian Disease Via Loss-Of-Function Variation, Alexander H. Li

Dissertations and Theses (Open Access)

A typical human exome harbors dozens of loss-of-function (LOF) variants predicted to severely disrupt or abolish gene function. These variants are enriched at the extremely rare end of the allele frequency spectrum (< 0.1%), suggesting purifying selection against these sites. However, most previous population-based sequencing studies have not included analysis of genotype-phenotype relationships with LOF variants. Thus, the contribution of LOF variation to health and disease within the general population remains largely uncharacterized.

Using whole exome sequence from 8,554 participants in the Atherosclerosis Risk in Communities (ARIC) study, we explored the impact of LOF variation on a broad spectrum of human phenotypes. First, we selected 20 common chronic disease risk factor phenotypes and performed gene-based association tests. Analysis of this sample verified two relationships in well-studied genes (PCSK9 and APOC3) and identified eight new loci. Novel relationships included …

Functional Analysis Of Synthetic Gene Circuits Controlling A Protein Pump In Yeast, Junchen Diao

Dissertations and Theses (Open Access)

Synthetic biology aims to build biological devices to understand living systems and explore new applications. Synthetic gene circuits such as genetic switches, oscillators and logic gates are at the core of many synthetic biology applications. These gene circuits often include a sensor/regulator protein capable to detect small molecules and then transduce them into a regulatory signal to generate measurable output. Similar signal transduction networks are also abundant in nature. However, in many natural and engineered scenarios, the output also affects the regulator/sensor protein. How such interactions between the regulator/sensor and the output affect synthetic gene circuit function has not been …

N-Acetylglucosamine Regulates Virulence Properties In Microbial Pathogens, Shamoon Naseem, James B. Konopka

Department of Molecular Genetics and Microbiology Faculty Publications

There is growing evidence that the sugar N-acetylglucosamine (GlcNAc) plays diverse roles in cell signaling pathways that impact the virulence properties of microbes and host cells. GlcNAc is already well known as a ubiquitous structural component at the cell surface that forms part of bacterial cell wall peptidoglycan, cell wall chitin in fungi and parasites, and extracellular matrix glycosaminoglycans of animal cells. Chitin and peptidoglycan have been previously linked to cell signaling as they can stimulate responses in plant and animal host cells [1–3]. Recent studies now indicate that GlcNAc released from these polymers can also …

Genome-Wide Meta-Analysis In Alopecia Areata Resolves Hla Associations And Reveals Two New Susceptibility Loci, Regina C. Betz, Lynn Petukhova, Stephan Ripke, Hailiang Huang, Androniki Menelaou, Silke Redeler, Tim Becker, Stefanie Heilmann, Tarek Yamany, Madeleine Duvic, Maria Hordinsky, David Norris, Vera H. Price, Julian Mackay-Wiggan, Annemieke De Jong, Gina M. Destefano, Susanne Moebus, Markus Böhm, Ulrike Blume-Peytavi, Hans Wolff, Gerhard Lutz, Roland Kruse, Li Bian, Christopher I. Amos

Dartmouth Scholarship

Alopecia areata (AA) is a prevalent autoimmune disease with ten known susceptibility loci. Here we perform the first meta-analysis in AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the MHC, where we fine-map 4 independent effects, all implicating HLA-DR as a key etiologic driver. Outside the MHC, we identify two novel loci that exceed statistical significance, containing ACOXL/BCL2L11(BIM) (2q13); GARP (LRRC32) (11q13.5), as well as a third nominally significant region SH2B3(LNK)/ ATXN2 (12q24.12). Candidate susceptibility gene expression …