Digital Commons Network^™

Human Gene Copy Number Spectra Analysis In Congenital Heart Malformations, Aoy Tomita-Mitchell, Donna K. Mahnke, Craig Struble, Maureen E. Tuffnell, Karl D. Stamm, Mats Hidestrand, Susan Harris, Mary A. Goetsch, Pippa Simpson, David P. Bick, Ulrich Broeckel, Andrew N. Pelech, James S. Tweddell, Michael Mitchell

Mathematics, Statistics and Computer Science Faculty Research and Publications

The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency “spectra” to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 …

Investing In Genetics, Bridger Feuz, Dillon M. Feuz

All Current Publications

Agriculture Extension professionals as well as other agriculture industry professionals often extol the virtues of being the” low cost producer.” In most cases being the low cost producer does lead to an increase in profitability. However, two different data sets have suggested a couple of areas that high profit producers actually spend more money on then low profit producers.

Pharmacists And Pharmacogenomics: An Evaluation Of Knowledge, Beliefs, Attitudes And Practices, Laressa Bethishou, Angela Chen, Chrissie Chew, Richard Dang, Courtney Greenber, Rebecca Ashlee Klevens, Vlada Treynker, Andrew Warnock, Melissa Durham, Jeffery A. Goad, Edith Mirzaian

Pharmacy Faculty Articles and Research

"Pharmacogenomics is the term used to describe the rapidly advancing study on how genetic makeup can impact drug therapy. In specialized clinical situations, such as the use of irinotecan in colon cancer or abacavir in HIV infections, it is now possible to identify specific genotypes that correlate strongly with a patient's therapeutic outcome, with implications on both efficacy and side effects. On a broader scale, a systematic review published by the Journal of the American Medical Association on the top 27 adverse reaction-causing drugs found that a majority of the adverse effects have a genetic component, suggesting that an analysis …

Pf19 Encodes The P60 Catalytic Subunit Of Katanin And Is Required For Assembly Of The Flagellar Central Apparatus In Chlamydomonas, Erin E. Dymek, Elizabeth F. Smith

Dartmouth Scholarship

For all eukaryotic cilia the basal bodies provide a template for the assembly of the doublet microtubules, and intraflagellar transport provides a mechanism for transport of axonemal components into the growing cilium. What is not known is how the central pair of microtubules is nucleated or how their associated polypeptides are assembled. Here we report that the Chlamydomonas pf19 mutation results in a single amino acid change within the p60 catalytic subunit of katanin, and that this mutation prevents microtubule severing activity. The pf19 mutant has paralyzed flagella that lack the central apparatus. Using a combination of mutant analysis, RNAi-mediated …

Dialogues, Dilemmas, And Disclosures: Genomic Research And Incidental Findings, Lynn W. Bush, Karen H. Rothenberg

Faculty Scholarship

No abstract provided.

Reducing False-Positive Prediction Of Minimotifs With A Genetic Interaction Filter, Jerlin Camilus Merlin, Sanguthevar Rajasekaran, Tian Mi, Martin Schiller

Life Sciences Faculty Research

Background

Minimotifs are short contiguous peptide sequences in proteins that have known functions. At its simplest level, the minimotif sequence is present in a source protein and has an activity relationship with a target, most of which are proteins. While many scientists routinely investigate new minimotif functions in proteins, the major web-based discovery tools have a high rate of false-positive prediction. Any new approach that reduces false-positives will be of great help to biologists.

Methods and Findings

We have built three filters that use genetic interactions to reduce false-positive minimotif predictions. The basic filter identifies those minimotifs where the source/target …

Transcriptional Regulation Of N-Acetylglutamate Synthase, Sandra Kirsch Heibel, Giselle Yvette Lopez, Maria Panglao, Sonal Sodha, Leonardo Marino-Ramirez, Mendel Tuchman, Ljubica Caldovic

Pediatrics Faculty Publications

The urea cycle converts toxic ammonia to urea within the liver of mammals. At least 6 enzymes are required for ureagenesis, which correlates with dietary protein intake. The transcription of urea cycle genes is, at least in part, regulated by glucocorticoid and glucagon hormone signaling pathways. N-acetylglutamate synthase (NAGS) produces a unique cofactor, N-acetylglutamate (NAG), that is essential for the catalytic function of the first and rate-limiting enzyme of ureagenesis, carbamyl phosphate synthetase 1 (CPS1). However, despite the important role of NAGS in ammonia removal, little is known about the mechanisms of its regulation. We identified two regions of high …

Genes And Plays: Bringing Elsi Issues To Life, Karen H. Rothenberg, Lynn W. Bush

Faculty Scholarship

Ethical complexities surround the promise of genomic technology and the power of genetic information as they alter conceptions of identity and dynamics within personal and professional relationships. Creative approaches such as dramatic vignettes offer a unique analytical stage for imagining the bioethical past and future. Dramatic narratives can bring to life images of differing perspectives and values when experiencing innovations in medicine. Although the scientific landscape shifts, concerns expressed in theatre from 50 years ago parallel many contemporary ELSI (ethical, legal and social implications) issues, highlighting the ongoing struggle to appreciate the impact of emerging genetic technologies on relationships. To …

Changing Language, Remaining Pygmy, Serge Bahuchet

Human Biology Open Access Pre-Prints

In this article I am illustrating the linguistic diversity of African Pygmy populations in order to better address their anthropological diversity and history. I am also introducing a new method, based on the analysis of specialized vocabulary, to reconstruct the substratum of some languages they speak. I show that Pygmy identity is not based on their languages, which have often been borrowed from neighboring non-Pygmy farmer communities with whom each Pygmy group is linked. Understanding the nature of this partnership, quite variable in history, is essential to address Pygmy languages, identity and history. Finally, I show that only a multidisciplinary …

Method For Screening For A Tobiano Coat Color Genotype, Ernest Bailey, Samantha A. Brooks

Veterinary Science Faculty Patents

A method for screening for a Tobiano genotype includes obtaining a nucleic acid from an equine animal, and analyzing the nucleic acid for the presence of an inversion in a chromosome ECA3q which is indicative of the genotype for Tobiano. The method includes detecting at least one of a telomeric breakpoint of an inverted ECA3q chromosome and/or a centromeric breakpoint of an inverted ECA3q chromosome. In one embodiment, the nucleic acid may be analyzed by the steps of hybridizing the group of probes or primers having the sequences set forth herein in SEQ ID NO:8, SEQ ID NO: 9, and …

Heterogeneity In Mitochondrial Morphology And Membrane Potential Is Independent Of The Nuclear Division Cycle In Multinucleate Fungal Cells, John P. Gerstenberger, Patricia Occhipinti, Amy S. Gladfelter

Dartmouth Scholarship

In the multinucleate filamentous fungus Ashbya gossypii, nuclei divide asynchronously in a common cytoplasm. We hypothesize that the division cycle machinery has a limited zone of influence in the cytoplasm to promote nuclear autonomy. Mitochondria in cultured mammalian cells undergo cell cycle-specific changes in morphology and membrane potential and therefore can serve as a reporter of the cell cycle state of the cytoplasm. To evaluate if the cell cycle state of nuclei in A. gossypii can influ

Doctors, Patients, And Pills--A System Popping Under Too Much Physician Discretion? A Law-Policy Prescription To Make Drug Approval More Meaningful In The Delivery Of Health Care, Michael J. Malinowski

Journal Articles

This article challenges the scope of physician discretion to engage in off-label use of prescription drugs. The discretion to prescribe dimensions beyond the clinical research that puts new drugs on pharmacy shelves has been shaped by two historic influences: a legacy of physician paternalism, solidarity, autonomy, and self-determination that predates the contemporary commercialization of medicine by more than half a century, and regulatory necessity due to the limits of science and innate crudeness of pharmaceuticals prior to the genomics revolution (drug development and delivery based upon genetic expression). Although both factors have changed immensely, the standard for drug approval has …

Genetics And Cancer, Sachin Puri

A with Honors Projects

Genes' effect in body and relationship with cancer. Role in cell cycle and angiogenesis.

Manipulating Fate: Medical Innovations, Ethical Implications, Theatrical Illuminations, Karen H. Rothenberg, Lynn W. Bush

Faculty Scholarship

Transformative innovations in medicine and their ethical complexities create frequent confusion and misinterpretation that color the imagination. Placed in historical context, theatre provides a framework to reflect upon how the ethical, legal, and social implications of emerging technologies evolve over time and how attempts to control fate through medical science have shaped -- and been shaped by -- personal and professional relationships. The drama of these human interactions is powerful and has the potential to generate fear, create hope, transform identity, and inspire empathy -- a vivid source to observe the complex implications of translating research into clinical practice through …

The Role Of Cax1 And Cax3 In Elemental Distribution And Abundance In Arabidopsis Seed, Tracy Punshon, Kendall Hirschi, Jian Yang, Antonio Lanzirotti, Barry Lai, Mary Lou Guerinot

Dartmouth Scholarship

The ability to alter nutrient partitioning within plants cells is poorly understood. In Arabidopsis (Arabidopsis thaliana), a family of endomembrane cation exchangers (CAXs) transports Ca²⁺ and other cations. However, experiments have not focused on how the distribution and partitioning of calcium (Ca) and other elements within seeds are altered by perturbed CAX activity. Here, we investigate Ca distribution and abundance in Arabidopsis seed from cax1 and cax3 loss-of-function lines and lines expressing deregulated CAX1 using synchrotron x-ray fluorescence microscopy. We conducted 7- to 10-μm resolution in vivo x-ray microtomography on dry mature seed and 0.2-μm resolution x-ray …

The Formin Fmnl3 Is A Cytoskeletal Regulator Of Angiogenesis, Clare Hetheridge, Alice N. Scott, Rajeeb K. Swain, John W. Copeland, Henry N. Higgs

Dartmouth Scholarship

The process of angiogenesis requires endothelial cells (ECs) to undergo profound changes in shape and polarity. Although this must involve remodelling of the EC cytoskeleton, little is known about this process or the proteins that control it. We used a co-culture assay of angiogenesis to examine the cytoskeleton of ECs actively undergoing angiogenic morphogenesis. We found that elongation of ECs during angiogenesis is accompanied by stabilisation of microtubules and their alignment into parallel arrays directed at the growing tip. In other systems, similar microtubule alignments are mediated by the formin family of cytoskeletal regulators. We screened a library of human …

Seg1 Controls Eisosome Assembly And Shape, Karen E. Moreira, Sebastian Schuck, Bianca Schrul, Florian Fröhlich, James B. Moseley

Dartmouth Scholarship

Eisosomes are stable domains at the plasma membrane of the budding yeast Saccharomyces cerevisiae and have been proposed to function in endocytosis. Eisosomes are composed of two main cytoplasmic proteins, Pil1 and Lsp1, that form a scaffold around furrow-like plasma membrane invaginations. We show here that the poorly characterized eisosome protein Seg1/Ymr086w is important for eisosome biogenesis and architecture. Seg1 was required for efficient incorporation of Pil1 into eisosomes and the generation of normal plasma membrane furrows. Seg1 preceded Pil1 during eisosome formation and established a platform for the assembly of other eisosome components. This platform was further shaped and …

Chapter 20: Pecan, Tommy E. Thompson, Patrick J. Conner

United States Department of Agriculture-Agricultural Research Service / University of Nebraska-Lincoln: Faculty Publications

The pecan, Carya illinoinensis (Wangenh.) K. Koch, is the most economically important member of the Carya genus and is the most valuable native North American nut crop. The Carya genus is a member of the walnut family, Juglandaceae, and comprises 20 species. Over 98% of the world’s annual pecan production is produced in the southern USA and northern Mexico. Pecan is a diploid (n = 16), monoecious, long-lived tree species. Owing to its heterodichogamy, pecan is primarily cross-pollinated, resulting in high heterozygosity with severe inbreeding depression when selfed. Establishment of commercial pecan orchards during the nineteenth century was mainly …

Olfactory Discrimination Predicts Cognitive Decline Among Community-Dwelling Older Adults, Hamid Sohrabi, Kristyn Bates, Mg Weinborn, A N Johnston, A Bahramian, Kevin Taddei, Simon Laws, Mark Rodrigues, Michael Morici, Matthew Howard, Georgia Martins, A Mackay-Sim, Se Gandy, Ralph Martins

Research outputs 2012

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions …

Genetic Measures Confirm Familial Relationships And Strengthen Study Design, Stacie J. Robinson, Ryan D. Walrath, Timonthy R. Vandeelen, Kurt C. Vercauteren

USDA Wildlife Services: Staff Publications

Social structure and behavioral interactions between individuals shape basic biological processes, such as breeding; foraging and predator avoidance; movement and dispersal; and disease transmission. We used a targeted trapping strategy to capture kin groups of white-tailed deer (Odocoileus virginianus) during 2007 and 2008 in Sandhill Wildlife Research Area, Wisconsin, USA, in order to observe social behaviors. Because inferring family relationships from observation of behavior is subjective, we usedmeasures of genetic relatedness and parentage assignment tests to determine that our capture strategy was efficient for capturing related pairs (78% of groups contained 1 dyad of related animals). The results of …

Tgfßriib Mutations Trigger Aortic Aneurysm Pathogenesis By Altering Transforming Growth Factor Ss2 Signal Transduction, Katherine J. Bee, David C. Wilkes, Richard B. Devereux, Craig T. Basson, Cathy J. Hatcher

PCOM Scholarly Papers

Background-Thoracic aortic aneurysm (TAA) is a common progressive disorder involving gradual dilation of the ascending and/or descending thoracic aorta that eventually leads to dissection or rupture. Nonsydromic TAA can occur as a genetically triggered, familial disorder that is usually transmitted in a monogenic autosomal dominant fashion and is known as familial TAA. Genetic analyses of families affected with TAA have identified several chromosomal loci, and further mapping of familial TAA genes has highlighted disease-causing mutations in at least 4 genes: myosin heavy chain 11 (MYH11), a-smooth muscle actin (ACTA2), and transforming growth factor ß receptors I and II (TGFßRI and …

Advancing Our Understanding Of The Inheritance And Transmission Of Pectus Excavatum, Lisa Horth, Michael W. Stacey, Virginia K. Proud, Kara Segna, Chelsea Rutherford, Donald Nuss, Robert E. Kelly

Bioelectrics Publications

Pectus excavatum is the most common congenital chest wall abnormality expressed in children, yet its inheritance is poorly understood. Here we present the first comprehensive assessment of the inheritance of this disorder. After evaluating 48 pedigrees and 56 clinical traits of probands and family members, we find strong evidence of autosomal recessive, genetic control for this disorder. Additionally there is likely more than one pectus disease-associated allele, as well as a relatively large number of disease allele carriers in the human population. Some clinical traits appear important and may serve as reliable indicators for predicting the likelihood of pectus excavatum …