Genetics and Genomics Commons^™

Hsp90 And Its Co-Chaperones Modify Tdp-43 Localization, Aggregation, And Toxicity, Lilian T. Lin

Electronic Thesis and Dissertation Repository

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with protein misfolding and protein aggregation. In particular, the TAR DNA-binding protein (TDP-43) is often found in the pathological inclusions in neurons of ALS patient brains and spinal cords. This phenomenon is known as TDP-43 proteinopathy, the mislocalization of TDP-43 from the cell nucleus and the formation of aggregates in the cytoplasm. Numerous mutations in the gene encoding TDP-43 have also been linked to familial cases of ALS (fALS) and cause TDP-43 proteinopathy. This study attempts to decipher how the molecular chaperone Hsp90 and its co-chaperones, Aha1, Sti1, and Cdc37, modulate …

Genetic Effect Of Drought On The California Newt, Taricha Torosa, Madeleine M. Perrault, Samantha Fiallo, Alero Arueyingho, Cindy Kim, Laiken Ritchie

Seaver College Research And Scholarly Achievement Symposium

Droughts are now a common occurrence in Southern California and are known to cause population declines in many species, and such bottlenecks can cause a loss of genetic variation. Genetic variation was examined in a population of the California newt located in Arroyo Sequit Creek in the Santa Monica Mountains. Genetic data from animals examined prior to the current drought were compared to similar data collected from the population after it experienced several years of severe drought. We hypothesized that the drought impacted population should show less genetic variation in comparison to the pre-drought population. Nevertheless, there were no genetic …

A Novel Multi-Network Approach Reveals Tissue-Specific Cellular Modulators Of Fibrosis In Systemic Sclerosis, Jaclyn N. Taroni, Casey S. Greene, Viktor Martyanov, Tammara A. Wood

Dartmouth Scholarship

Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology.We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast …

Whole Transcriptome Comparison Between Multipotent Adult Stem Cells (Mascs) And Two Families Of Mesenchymal Stem Cells (Mscs), Jessica C. Black, Drew Cumming, Andra Sullivan, Wei-Hua Huang, Paul A. Lucas

NYMC Faculty Posters

No abstract provided.

Demethylated Hsatii Dna And Hsatii Rna Foci Sequester Prc1 And Mecp2 Into Cancer-Specific Nuclear Bodies, L. L. Hall, M. Byron, Dawn M. Carone, T. W. Whitfield, G. P. Pouliot, A. Fischer, P. Jones, J. B. Lawrence

Biology Faculty Works

This study reveals that high-copy satellite II (HSATII) sequences in the human genome can bind and impact distribution of chromatin regulatory proteins and that this goes awry in cancer. In many cancers, master regulatory proteins form two types of cancer-specific nuclear bodies, caused by locus-specific deregulation of HSATII. DNA demethylation at the 1q12 mega-satellite, common in cancer, causes PRC1 aggregation into prominent Cancer-Associated Polycomb (CAP) bodies. These loci remain silent, whereas HSATII loci with reduced PRC1 become derepressed, reflecting imbalanced distribution of UbH2A on these and other PcG-regulated loci. Large nuclear foci of HSATII RNA form and sequester copious MeCP2 …

Species Delimitation And Lineage Separation History Of A Species Complex Of Aspens In China, Honglei Zheng, Liqiang Fan, Richard I. Milne, Lei Zhang, Yaling Wang, Kangshan Mao

Aspen Bibliography

Species delimitation in tree species is notoriously challenging due to shared polymorphisms among species. An integrative survey that considers multiple operational criteria is a possible solution, and we aimed to test it in a species complex of aspens in China. Genetic [four chloroplast DNA (cpDNA) fragments and 14 nuclear microsatellite loci (nSSR)] and morphological variations were collected for 76 populations and 53 populations, respectively, covering the major geographic distribution of the Populus davidiana-rotundifoliacomplex. Bayesian clustering, analysis of molecular variance (AMOVA), Principle Coordinate Analysis (PCoA), ecological niche modeling (ENM), and gene flow (migrants per generation), were employed to …

Mirnas Associated With Prostate Cancer Risk And Progression, Hung N. Luu, Hui-Yi Lin, Karina Dalsgaard Sorensen, Olorunseun O. Ogunwobi, Nagi Kumar, Ganna Chornokur, Catherine Phelan, Dominique Jones, Lacreis Kidd, Jyotsna Batra, Kosj Yamoah, Anders Berglund, Robert J. Rounbehler, Mihi Yang, Sang Haak Lee, Nahyeon Kang, Seung Joon Kim, Jong Y. Park, Giuliano Di Pietro

Publications and Research

Prostate cancer is the most common malignancy among men in the US. Though considerable improvement in the diagnosis of prostate cancer has been achieved in the past decade, predicting disease outcome remains a major clinical challenge. Recent expression profiling studies in prostate cancer suggest microRNAs (miRNAs) may serve as potential biomarkers for prostate cancer risk and disease progression. miRNAs comprise a large family of about 22-nucleotide-long non-protein coding RNAs, regulate gene expression post-transcriptionally and participate in the regulation of numerous cellular processes. In this review, we discuss the current status of miRNA in studies evaluating the disease progression of prostate …

Mechanism For Microbial Population Collapse In A Fluctuating Resource Environment., Serdar Turkarslan, Arjun V Raman, Anne W Thompson, Christina E Arens, Mark A Gillespie, Frederick Von Netzer, Kristina L Hillesland, Sergey Stolyar, Adrián López García De Lomana, David J Reiss, Drew Gorman-Lewis, Grant M Zane, Jeffrey A Ranish, Judy D Wall, David A Stahl, Nitin Baliga

Articles, Abstracts, and Reports

Managing trade-offs through gene regulation is believed to confer resilience to a microbial community in a fluctuating resource environment. To investigate this hypothesis, we imposed a fluctuating environment that required the sulfate-reducer

Coccolithoviruses: A Review Of Cross-Kingdom Genomic Thievery And Metabolic Thuggery, Jozef I. Nissimov, António Pagarete, Fangrui Ma, Sean Cody, David D. Dunigan, Susan A. Kimmance, Michael J. Allen

Nebraska Center for Virology: Faculty Publications

Coccolithoviruses (Phycodnaviridae) infect and lyse the most ubiquitous and successful coccolithophorid in modern oceans, Emiliania huxleyi. So far, the genomes of 13 of these giant lytic viruses (i.e., Emiliania huxleyi viruses—EhVs) have been sequenced, assembled, and annotated. Here, we performed an in-depth comparison of their genomes to try and contextualize the ecological and evolutionary traits of these viruses. The genomes of these EhVs have from 444 to 548 coding sequences (CDSs). Presence/absence analysis of CDSs identified putative genes with particular ecological significance, namely sialidase, phosphate permease, and sphingolipid biosynthesis. The viruses clustered into distinct clades, based on their DNA polymerase …

Discovery And Validation Of Information Theory-Based Transcription Factor And Cofactor Binding Site Motifs., Ruipeng Lu, Eliseos J Mucaki, Peter K Rogan

Biochemistry Publications

Data from ChIP-seq experiments can derive the genome-wide binding specificities of transcription factors (TFs) and other regulatory proteins. We analyzed 765 ENCODE ChIP-seq peak datasets of 207 human TFs with a novel motif discovery pipeline based on recursive, thresholded entropy minimization. This approach, while obviating the need to compensate for skewed nucleotide composition, distinguishes true binding motifs from noise, quantifies the strengths of individual binding sites based on computed affinity and detects adjacent cofactor binding sites that coordinate with the targets of primary, immunoprecipitated TFs. We obtained contiguous and bipartite information theory-based position weight matrices (iPWMs) for 93 sequence-specific TFs, …

Latexin Inactivation Enhances Survival And Long-Term Engraftment Of Hematopoietic Stem Cells And Expands The Entire Hematopoietic System In Mice, Yi Liu, Cuiping Zhang, Zhenyu Li, Chi Wang, Jianhang Jia, Tianyan Gao, Gerhard C. Hildebrandt, Daohong Zhou, Subbarao Bondada, Peng Ji, Daret K. St. Clair, Jinze Liu, Chang-Guo Zhan, Hartmut Geiger, Shuxia Wang, Ying Liang

Toxicology and Cancer Biology Faculty Publications

Natural genetic diversity offers an important yet largely untapped resource to decipher the molecular mechanisms regulating hematopoietic stem cell (HSC) function. Latexin (Lxn) is a negative stem cell regulatory gene identified on the basis of genetic diversity. By using an Lxn knockout mouse model, we found that Lxn inactivation in vivo led to the physiological expansion of the entire hematopoietic hierarchy. Loss of Lxn enhanced the competitive repopulation capacity and survival of HSCs in a cell-intrinsic manner. Gene profiling of Lxn-null HSCs showed altered expression of genes enriched in cell-matrix and cell-cell interactions. Thrombospondin 1 (Thbs1 …

Draft Genome Sequence Of Cercospora Sojina Isolate S9, A Fungus Causing Frogeye Leaf Spot (Fls) Disease Of Soybean, Fanchang Zeng, Chaofan Wang, Guirong Zhang, Junmei Wei, Carl A. Bradley, Ray Ming

Plant Pathology Faculty Publications

Fungi are the causal agents of many of the world's most serious plant diseases causing disastrous consequences for large-scale agricultural production. Pathogenicity genomic basis is complex in fungi as multicellular eukaryotic pathogens. The fungus Cercospora sojina is a plant pathogen that threatens global soybean supplies. Here, we report the genome sequence of C. sojina strain S9 and detect genome features and predicted genomic elements. The genome sequence of C. sojina is a valuable resource with potential in studying the fungal pathogenicity and soybean host resistance to frogeye leaf spot (FLS), which is caused by C. sojina. …

Development Of Near-Isogenic Lines In A Parthenogenetically Reproduced Thrips Species, Frankliniella Occidentalis, Guangdi Yuan, Yanran Wan, Xiaoyu Li, Bingqing He, Youjun Zhang, Baoyun Xu, Shaoli Wang, Wen Xie, Xuguo Zhou, Qingjun Wu

Entomology Faculty Publications

Although near-isogenic lines (NILs) can standardize genetic backgrounds among individuals, it has never been applied in parthenogenetically reproduced animals. Here, through multiple rounds of backcrossing and spinosad screening, we generated spinosad resistant NILs in the western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), with a haplo-diploid reproduction system. The resultant F. occidentalis NIL-R strain maintained a resistance ratio over 30,000-fold, which was comparable to its parental resistant strain, Spin-R. More importantly, F. occidentalis NIL-R shared 98.90% genetic similarity with its susceptible parental strain Ivf03. By developing this toolset, we are able to segregate individual resistance and facilitate the mechanistic study …

Transcriptome Approach For Identifying Potential Biomarkers For Endocrine Disruption Due To Crude Oil Exposure Using Killifish (Fundulus Heteroclitus)., Frank J. Zadlock Iv

Seton Hall University Dissertations and Theses (ETDs)

The killifish, Fundulus heteroclitus, is a common fish model in aquatic toxicology. However, little is known in this organism about how endocrine disrupting compounds, (EDCs) including polycyclic aromatic hydrocarbons (PAHs), impact the reproductive status from a molecular standpoint. The objective of this project is to apply high throughput sequencing to F. heteroclitus testes to examine the molecular mechanisms that impair reproduction when exposed to crude oil. First, a crude oil exposure experiment was conducted. Following exposure, semi-quantitative PCR was performed to detect changes in gene expression of the following genes known to respond to EDCs: gonadal aromatase (CYP19a), vitellogenin …

P08. Unravelling Organelle Genome Evolution Architecture Using Rna-Sequencing Data, Matheus Sanita Lima, David Roy Smith

Western Research Forum

Background: Mitochondria genomes vary from 11 Mb to 6 kb, while plastids can vary from 1 Mb to 30 kb. Non-coding DNA accounts for most of this size variation, but the mechanistic and evolutionary reasons for that are still unknown. Next generation sequencing has generated unprecedented amounts of genomic and transcriptomic data that can be used for organelle genome evolution studies. However, most of these data is used only for the study of cell nucleus. Therefore, I decided to use these untapped data source to investigate the transcription of organelle genomes in plastid-bearing protists.

Methods: I mapped the transcriptomes over …

P02. Production Of A Protein Subunit Vaccine For Mannheimia Haemolytica In Lettuce Chloroplasts, Coby K. Martin

Western Research Forum

The cattle industry worldwide is ravaged by bovine respiratory disease (BRD), a bacterial disease caused by Mannheimia haemolytica. We have designed a chimeric protein subunit vaccine against M. haemolytica based on recent evidence demonstrating the protective potential of antigens against a virulence factor, leukotoxin, in addition to a surface lipoprotein. Plant-based production of this protein vaccine provides a safe and inexpensive alternative to traditional production methods. Plant-base production also supports the use of an edible vaccine that will deliver antigens to pharyngeal tissues to provide local immunization against M. haemolytica to prior to its progression into the lungs. Chloroplasts …

Genome Sequencing Of The Sweetpotato Whitefly Bemisia Tabaci Med/Q, Wen Xie, Chunhai Chen, Zezhong Yang, Litao Guo, Xin Yang, Dan Wang, Ming Chen, Jinqun Huang, Yanan Wen, Yang Zeng, Yating Liu, Jixing Xia, Lixia Tian, Hongying Cui, Qingjun Wu, Shaoli Wang, Baoyun Xu, Xianchun Li, Xinqiu Tan, Murad Ghanim, Baoli Qiu, Huipeng Pan, Dong Chu, Helene Delatte, M. N. Maruthi, Feng Ge, Xueping Zhou, Xiaowei Wang, Fanghao Wan, Yuzhou Du, Xuguo Joe Zhou

Entomology Faculty Publications

The sweetpotato whitefly Bemisia tabaci is a highly destructive agricultural and ornamental crop pest. It damages host plants through both phloem feeding and vectoring plant pathogens. Introductions of B. tabaci are difficult to quarantine and eradicate because of its high reproductive rates, broad host plant range, and insecticide resistance. A total of 791 Gb of raw DNA sequence from whole genome shotgun sequencing, and 13 BAC pooling libraries were generated by Illumina sequencing using different combinations of mate-pair and pair-end libraries. Assembly gave a final genome with a scaffold N50 of 437 kb, and a total length of 658 Mb. …

Complete Genome Sequence Of Spiroplasma Sp. Nbrc 100390, Mindia Haryono, Wen-Sui Lo, Gail E. Gasparich, Chih-Horng Kuo

Gail Gasparich

Apolipoprotein E4 And Insulin Resistance Interact To Impair Cognition And Alter The Epigenome And Metabolome, Lance A. Johnson, Eileen Ruth S. Torres, Soren Impey, Jan F. Stevens, Jacob Raber

Physiology Faculty Publications

Apolipoprotein E4 (E4) and type 2 diabetes are major risk factors for cognitive decline and late onset Alzheimer’s disease (AD). E4-associated phenotypes and insulin resistance (IR) share several features and appear to interact in driving cognitive dysfunction. However, shared mechanisms that could explain their overlapping pathophysiology have yet to be found. We hypothesized that, compared to E3 mice, E4 mice would be more susceptible to the harmful cognitive effects of high fat diet (HFD)-induced IR due to apoE isoform-specific differences in brain metabolism. While both E3 and E4 mice fed HFD displayed impairments in peripheral metabolism and cognition, deficits in …

Molecular Regulation Of Stem Cell Behavior During Tissue Repair And Cancer Formation, Nestor J. Oviedo

Science Seminar Series

Oviedo will be presenting his work on identifying the mechanisms of adult stem cell fate determination based on their topographical location in the adult body. Understanding stem cell fate determination is crucial because tissue repair and neoplastic growth are greater in anterior than in posterior regions of adult animals. Despite its critical implications for stem cell biology, carcinogenesis and regenerative medicine, this physiological phenomenon has remained overlooked. Recent findings from his group provide intriguing evidence implying DNA repair mechanisms and cellular signaling through post-translational modifications regulate stem cell fate decision depending on their topographical location in the adult body. We …