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2019

Genetics

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Articles 1 - 30 of 38

Full-Text Articles in Life Sciences

Mutations In The Sptlc1 Gene Are A Cause Of Amyotrophic Lateral Sclerosis That May Be Amenable To Serine Supplementation, Janel O. Johnson, Ruth Chia, Robert H. Brown Jr., John E. Landers Sep 2019

Mutations In The Sptlc1 Gene Are A Cause Of Amyotrophic Lateral Sclerosis That May Be Amenable To Serine Supplementation, Janel O. Johnson, Ruth Chia, Robert H. Brown Jr., John E. Landers

University of Massachusetts Medical School Faculty Publications

SPTLC1 encodes a critical subunit of serine palmitoyltransferase, the enzyme catalyzing the first and rate-limiting step in de novo sphingolipid biosynthesis, and mutations in this gene are known to cause hereditary sensory autonomic neuropathy, type 1A. Using exome sequencing, we identified a de novo variant in SPTLC1 resulting in a p.Ala20Ser amino acid change in an individual diagnosed with juvenile-onset amyotrophic lateral sclerosis (ALS) and confirmed its pathogenicity by showing elevated plasma levels of neurotoxic deoxymethyl-sphinganine. A second case of juvenile-onset ALS arising again from a p.Ala20Ser mutation was later identified, confirming the association of SPTLC1 with this ...


Signaling To Trp53 And Tap63 From Chk1/Chk2 Is Responsible For Elimination Of Most Oocytes Defective For Either Chromosome Synapsis Or Recombination, Vera D. Rinaldi, Jordana C. Bloom, John C. Schimenti Sep 2019

Signaling To Trp53 And Tap63 From Chk1/Chk2 Is Responsible For Elimination Of Most Oocytes Defective For Either Chromosome Synapsis Or Recombination, Vera D. Rinaldi, Jordana C. Bloom, John C. Schimenti

University of Massachusetts Medical School Faculty Publications

Eukaryotic organisms have evolved mechanisms to prevent the accumulation of cells bearing genetic aberrations. This is especially crucial for the germline, because fecundity, and fitness of progeny would be adversely affected by an excessively high mutational incidence. The process of meiosis poses unique problems for mutation avoidance, due to the requirement for SPO11-induced programmed double strand breaks (DSBs) in recombination-driven pairing and segregation of homologous chromosomes. Mouse meiocytes bearing unrepaired meiotic DSBs or unsynapsed chromosomes are eliminated before completing meiotic prophase I. In previous work, we showed that checkpoint kinase 2 (CHK2; CHEK2), a canonical DNA damage response protein, is ...


9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association Sep 2019

9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

MD Anderson Cancer Center Postdoctoral Association Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.


Rare Degs1 Variant Significantly Alters De Novo Ceramide Synthesis Pathway, Nicholas B. Blackburn, Joanne E. Curran, Laura F. Michael, Peter J. Meikle, Juan M. Peralta, Marian Mosio, Scott Mcahern, Hai H. Bui, Melissa A. Bellinger, Corey Giles, Satish Kumar, Ana C. Leandro, Marcio Alameida, Jacquelyn M. Weir, Michael C. Mahaney, Thomas D. Dyer, Laura Almasy, John L. Vandeberg, Sarah Williams-Blangero, David C. Glahn, Ravindranath Duggirala, Mark Kowola, John Blangero Sep 2019

Rare Degs1 Variant Significantly Alters De Novo Ceramide Synthesis Pathway, Nicholas B. Blackburn, Joanne E. Curran, Laura F. Michael, Peter J. Meikle, Juan M. Peralta, Marian Mosio, Scott Mcahern, Hai H. Bui, Melissa A. Bellinger, Corey Giles, Satish Kumar, Ana C. Leandro, Marcio Alameida, Jacquelyn M. Weir, Michael C. Mahaney, Thomas D. Dyer, Laura Almasy, John L. Vandeberg, Sarah Williams-Blangero, David C. Glahn, Ravindranath Duggirala, Mark Kowola, John Blangero

School of Medicine Publications and Presentations

The de novo ceramide synthesis pathway is essential to human biology and health but genetic influences remain unexplored. The core function of this pathway is the generation of biologically active ceramide from its precursor, dihydroceramide. Dihydroceramides have diverse, often protective, biological roles; conversely, increased ceramide levels are biomarkers of complex disease. To explore the genetics of the ceramide synthesis pathway, we searched for deleterious nonsynonymous variants in the genomes of 1,020 Mexican Americans from extended pedigrees. We identified a Hispanic ancestry−specific rare functional variant, L175Q, in DEGS1, a key enzyme in the pathway that converts dihydroceramide to ceramide ...


Origins Of An Unmarked Georgia Cemetery Using Ancient Dna Analysis, Andrew T. Ozga, Raul Y. Tito, Brian M. Kemp, Hugh Matternes, Alexandra J. Obregon-Tito, Leslie Neal, Cecil M. Lewis Jr. Aug 2019

Origins Of An Unmarked Georgia Cemetery Using Ancient Dna Analysis, Andrew T. Ozga, Raul Y. Tito, Brian M. Kemp, Hugh Matternes, Alexandra J. Obregon-Tito, Leslie Neal, Cecil M. Lewis Jr.

Andrew Ozga

Determining the origins of those buried within undocumented cemeteries is of incredible importance to historical archaeologists and, in many cases, the nearby communities. In the case of Avondale Burial Place, a cemetery in Bibb County, Georgia, in use from 1820 to 1950, all written documentation of those interred within it has been lost. Osteological and archaeological evidence alone could not describe, with confidence, the ancestral origins of the 101 individuals buried there. In the present study, we used ancient DNA extraction methods in well-preserved skeletal fragments from 20 individuals buried in Avondale Burial Place to investigate the origins of the ...


Gain-Of-Function Mutations In The Unc-2/Cav2alpha Channel Lead To Excitation-Dominant Synaptic Transmission In C. Elegans, Yung-Chi Huang, Jennifer K. Pirri, Diego Rayes, Shangbang Gao, Ben Mulcahy, Jeff Grant, Yasunori Saheki, Michael M. Francis, Mei Zhen, Mark J. Alkema Aug 2019

Gain-Of-Function Mutations In The Unc-2/Cav2alpha Channel Lead To Excitation-Dominant Synaptic Transmission In C. Elegans, Yung-Chi Huang, Jennifer K. Pirri, Diego Rayes, Shangbang Gao, Ben Mulcahy, Jeff Grant, Yasunori Saheki, Michael M. Francis, Mei Zhen, Mark J. Alkema

Neurobiology Publications and Presentations

Mutations in pre-synaptic voltage gated calcium channels can lead to familial hemiplegic migraine type 1 (FHM1). While mammalian studies indicate that the migraine brain is hyperexcitable due to enhanced excitation or reduced inhibition, the molecular and cellular mechanisms underlying this excitatory/inhibitory (E/I) imbalance are poorly understood. We identified a gain-of-function (gf) mutation in the Caenorhabditis elegans CaV2 channel alpha1 subunit, UNC-2, which leads to increased calcium currents. unc-2(zf35gf) mutants exhibit hyperactivity and seizure-like motor behaviors. Expression of the unc-2 gene with FHM1 substitutions R192Q and S218L leads to hyperactivity similar to that of unc-2(zf35gf) mutants. unc-2 ...


Common Variants In The Glycerol Kinase Gene Reduce Tuberculosis Drug Efficacy, Michelle M. Bellerose, Seung-Hun Baek, Chuan-Chin Huang, Caitlin E. Moss, Eun-Ik Koh, Megan K. Proulx, Clare M. Smith, Richard E. Baker, Jong Seok Lee, Seokyong Eum, Sung Jae Shin, Sang-Nae Cho, Megan Murray, Christopher M. Sassetti Jul 2019

Common Variants In The Glycerol Kinase Gene Reduce Tuberculosis Drug Efficacy, Michelle M. Bellerose, Seung-Hun Baek, Chuan-Chin Huang, Caitlin E. Moss, Eun-Ik Koh, Megan K. Proulx, Clare M. Smith, Richard E. Baker, Jong Seok Lee, Seokyong Eum, Sung Jae Shin, Sang-Nae Cho, Megan Murray, Christopher M. Sassetti

Open Access Articles

Despite the administration of multiple drugs that are highly effective in vitro, tuberculosis (TB) treatment requires prolonged drug administration and is confounded by the emergence of drug-resistant strains. To understand the mechanisms that limit antibiotic efficacy, we performed a comprehensive genetic study to identify Mycobacterium tuberculosis genes that alter the rate of bacterial clearance in drug-treated mice. Several functionally distinct bacterial genes were found to alter bacterial clearance, and prominent among these was the glpK gene that encodes the glycerol-3-kinase enzyme that is necessary for glycerol catabolism. Growth on glycerol generally increased the sensitivity of M. tuberculosis to antibiotics in ...


Science, Physiology, And Nutrition For The Nonscientist, Judi S. Morrill Jul 2019

Science, Physiology, And Nutrition For The Nonscientist, Judi S. Morrill

Open Educational Resources

A wonderful blend of physiology, nutrition, biochemistry, genetics, biology, evolution, chemistry--what we all need to know as informed citizens. A basic knowledge of the life sciences and how our bodies work--to promote our own good health, especially as we're bombarded with misleading advertisements, soundbites, and the like. DNA fingerprinting, calorie requirements, dietary advice, genetic engineering (including gene editing with CRISPR cas9)--all in an easy-to understand book.


Hierarchical Modeling And Differential Expression Analysis For Rna-Seq Experiments With Inbred And Hybrid Genotypes, Andrew Lithio, Dan Nettleton Jul 2019

Hierarchical Modeling And Differential Expression Analysis For Rna-Seq Experiments With Inbred And Hybrid Genotypes, Andrew Lithio, Dan Nettleton

Dan Nettleton

The performance of inbred and hybrid genotypes is of interest in plant breeding and genetics. High-throughput sequencing of RNA (RNA-seq) has proven to be a useful tool in the study of the molecular genetic responses of inbreds and hybrids to environmental stresses. Commonly used experimental designs and sequencing methods lead to complex data structures that require careful attention in data analysis. We demonstrate an analysis of RNA-seq data from a split-plot design involving drought stress applied to two inbred genotypes and two hybrids formed by crosses between the inbreds. Our generalized linear modeling strategy incorporates random effects for whole-plot experimental ...


Engineering Mankind: The Sociopolitical Impact Of Eugenics In America, Megan Lee Jun 2019

Engineering Mankind: The Sociopolitical Impact Of Eugenics In America, Megan Lee

Voces Novae

During the early twentieth century, the American eugenics movement prospered, spreading its influence within the sociopolitical framework of the United States. The notion of eugenics – the control of human breeding to increase desirable traits, was extensively propagated through the creation of sterilization laws and public programs. Eventually, the public came to view eugenics as a necessity in order to preserve and improve the quality of mankind for the future.


Adaptive Evolution Targets A Pirna Precursor Transcription Network, Swapnil S. Parhad, Tianxiong Yu, Gen Zhang, Nicholas P. Rice, Zhiping Weng, William E. Theurkauf Jun 2019

Adaptive Evolution Targets A Pirna Precursor Transcription Network, Swapnil S. Parhad, Tianxiong Yu, Gen Zhang, Nicholas P. Rice, Zhiping Weng, William E. Theurkauf

University of Massachusetts Medical School Faculty Publications

In Drosophila, transposon-silencing piRNAs are derived from heterochromatic clusters and a subset of euchromatic transposon insertions, which are transcribed from internal non-canonical initiation sites and flanking canonical promoters. Rhino binds to Deadlock, which recruits TRF2 to promote non-canonical transcription of these loci. Cuff co-localizes with Rhino and Del. The role of Cuff is less well understood, but the cuff gene shows hallmarks of adaptive evolution, which frequently targets functional interactions within host defense systems. We show that Drosophila simulans cuff is a dominant negative allele when expressed in Drosophila melanogaster, where it traps Deadlock, TRF2 and the transcriptional co-repressor CtBP ...


Genetic Sequencing For Measuring Biodiversity In Recent And Ancient Marine Sediments, Lauren Judge May 2019

Genetic Sequencing For Measuring Biodiversity In Recent And Ancient Marine Sediments, Lauren Judge

Celebration of Learning

Taxonomic biodiversity, measured by counting the number of species present in a given area, is the most common method of capturing ecosystem biodiversity in recent and ancient environments. While this method is widely accepted, it is limited by poor preservation and identification of many individuals, making it impossible to include every species within an ecosystem and resulting in the loss of some diversity information. To address this issue, we measured the genetic biodiversity (in which species are determined based on sequencing of their DNA) of shallow marine ecosystems by extracting and sequencing the 18S ribosomal gene from bulk carbonate sediment ...


Genetic Crosstalk And Its Effects On Virulence And Mating In Ustilago Maydis., John S. Desmarais May 2019

Genetic Crosstalk And Its Effects On Virulence And Mating In Ustilago Maydis., John S. Desmarais

College of Arts & Sciences Senior Honors Theses

Ustilago maydis is a model organism for study of fungal mating and host infection. Two compatible haploid mating types must mate to form a dikaryon in order for the fungus to infect its host, corn (Zea mays). There are a variety of genetic mechanisms that regulate mating and infection in the fungus, many of which coregulate both processes. The aim of this study was to investigate how alteration of certain regulatory proteins in U. maydis affects these basic processes as well as how alteration of genes involved in signaling pathways can affect the expression of one another. Primarily, the focus ...


Surveying Apicomplexan Diversity And Dynamics In Narragansett Bay, Evelyn Spencer May 2019

Surveying Apicomplexan Diversity And Dynamics In Narragansett Bay, Evelyn Spencer

Senior Honors Projects

Parasites play an important role in marine ecosystems and their diversity is generally understudied. Apicomplexans, a group of parasitic protists in the phylum Alveolata, infect a wide variety of animal hosts and are abundant in ecosystems spanning from Polar Regions to Neotropical rainforests. Previous data generated from marine sediments in Antarctica, Naples Bay, and off the coast of Oslo, exhibit high diversity and numbers of apicomplexans. Abundance and diversity of these protists are unknown for Narragansett Bay, despite the fact that they infect many commercially important species. The aim of my study was to obtain abundance data and understand genetic ...


What Can We Do? Puzzling Over The Interpretation Of Heredity And Variation From Galton To Genetic Engineering, Peter J. Taylor May 2019

What Can We Do? Puzzling Over The Interpretation Of Heredity And Variation From Galton To Genetic Engineering, Peter J. Taylor

Working Papers on Science in a Changing World

First six chapters of a book motivated as follows: When I had mentioned to colleagues that I was exploring some significant issues overlooked by both sides in nature-nurture debates, the typical response was “we know, of course, that nature and nurture are intertwined”; they never asked “which nature-nurture science are you referring to?” It occurred to me that, in the long history of nature-nurture debates, opposing sides had always assumed or implied that these different scientific approaches were speaking to the same issues. If that were the case, then the challenge—something I was already puzzling over—was how best ...


The Role Of T-Cell Lymphoma Invasion And Metastasis 2 (Tiam2) In The Barrier Function Of Mammary Epithelial Cells Following Streptococcus Uberis Inoculation, Catherine E. Donnell May 2019

The Role Of T-Cell Lymphoma Invasion And Metastasis 2 (Tiam2) In The Barrier Function Of Mammary Epithelial Cells Following Streptococcus Uberis Inoculation, Catherine E. Donnell

Chancellor’s Honors Program Projects

No abstract provided.


Detection Of Heteroplasmic Single Nucleotide Polymorphisms Using Melt Curve Analysis And Dual Labeled Fluorescent Probes, Emily Jezewski Apr 2019

Detection Of Heteroplasmic Single Nucleotide Polymorphisms Using Melt Curve Analysis And Dual Labeled Fluorescent Probes, Emily Jezewski

Honors Theses, University of Nebraska-Lincoln

Plant mitochondrial genomes are strange – they are unusually large, consist of huge amounts of non-coding DNA, and contain of several overlapping regions throughout the genome. The genome is made of several different sized linear and circular molecules and different mitochondria within a cell will have different pieces of the genome. Even if multiple mitochondria contain the same region of the genome, these sequences can differ by single nucleotide polymorphisms (SNPS). This is known as heteroplasmy. Heteroplasmy has been documented in Arabidopsis thaliana using whole-genome sequencing data. While heteroplasmy is well-documented, its existence in the mitochondrial genome is unexpected and it ...


Double Gene Knockout Of Pdx-1 And Hnf1Β Leads To Possible Novel Gene Therapy For Type 1 Diabetes, Kathryn Kosiorek Apr 2019

Double Gene Knockout Of Pdx-1 And Hnf1Β Leads To Possible Novel Gene Therapy For Type 1 Diabetes, Kathryn Kosiorek

Spring Showcase for Research and Creative Inquiry

Diabetes Mellitus is a disease characterized by uncontrolled and elevated blood glucose which is the effect of inadequate levels of plasma insulin. Type I diabetes (T1D) ultimately stems from the autoimmune destruction of beta cells because of defects in the PDX-1 and possibly HNF1B. If both of these genes knocked out together increase the detriment effect of T1D, then a gene therapy can be created using the AAV vectors that not only targets one gene but both at the same time, increasing the strength of the gene therapy and the quality of life for the T1D patient.


Plant Mitochondrial Genome Evolution And Structure Has Been Shaped By Double-Strand Break Repair And Recombination, Emily Wynn Apr 2019

Plant Mitochondrial Genome Evolution And Structure Has Been Shaped By Double-Strand Break Repair And Recombination, Emily Wynn

Dissertations and Theses in Biological Sciences

Plant mitochondrial genomes are large but contain a small number of genes. These genes have very low mutation rates, but genomes rearrange and expand at significant rates. We propose that much of the apparent complexity of plant mitochondrial genomes can be explained by the interactions of double-strand break repair, recombination, and selection. One possible explanation for the disparity between the low mutation rates of genes and the high divergence of non-genes is that synonymous mutations in genes are not truly neutral. In some species, rps14 has been duplicated in the nucleus, allowing the mitochondrial copy to become a pseudogene. By ...


X-Inactivation And Epigenetics, Serena Weston Apr 2019

X-Inactivation And Epigenetics, Serena Weston

Thinking Matters Symposium

To prevent abnormal development caused by expressing both X chromosomes, female mammals inactivate one of their X chromosomes using an epigenetic process called dosage compensation. This literature review examines how X chromosome inactivation (XCI) occurs during the formation and development of an embryo. This condensation of DNA is marked by histone tail modifications, DNA methylation, and the arrival of structural proteins resulting in extraordinarily stable heterochromatin. X-inactivation is regulated in cis by the X-inactivation center (Xic) that contains the Xist gene and its antisense gene, Tsix. On one X chromosome, Xist RNA is expressed and coats the center of the ...


The Influence Of Stressful Life Events On The Development Of Type 2 Diabetes, Joshua Minks Mar 2019

The Influence Of Stressful Life Events On The Development Of Type 2 Diabetes, Joshua Minks

Dissertations

This study examined the relationship between distress and the development of Type 2 diabetes mellitus (T2DM) in the presence of established risk factors. Distress secondary to mental health disparities, stressful life events, and work conditions has been shown to promote insulin resistance and the development of T2DM.

Subjects (N=79) diagnosed with T2DM within the previous six months were recruited from SSM Health Centers and VA Medical Centers in the greater St. Louis area. They completed the Recent Life Changes Questionnaire, ENRICHD Social Support Instrument, and a demographic survey and analyses were conducted to determine differences between the veteran and ...


Toward A Rhetoric Of Dna: The Advent Of Crispr, Michael J. Zerbe Feb 2019

Toward A Rhetoric Of Dna: The Advent Of Crispr, Michael J. Zerbe

Poroi

The nucleic acid DNA, which contains an organism’s genetic information, consists of a four-letter alphabet that has until recently been characterized as a read-only text. The development of a quick, inexpensive DNA targeting and manipulation technique called CRISPR, pronounced “crisper,” though, has changed DNA from this arhetorical, read-only data set, as it has been characterized in the rhetoric literature to date, to a fully rhetorical text—one that can be not only read but created, interpreted, copied, altered, and stored as well. The Book of Nature, an idea with roots in antiquity but popularized during the nineteenth century, provides ...


Mutations In The Glycosyltransferase Domain Of Glt8d1 Are Associated With Familial Amyotrophic Lateral Sclerosis, Johnathan Cooper-Knock, John E. Landers, Pamela J. Shaw Feb 2019

Mutations In The Glycosyltransferase Domain Of Glt8d1 Are Associated With Familial Amyotrophic Lateral Sclerosis, Johnathan Cooper-Knock, John E. Landers, Pamela J. Shaw

Open Access Articles

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder without effective neuroprotective therapy. Known genetic variants impair pathways, including RNA processing, axonal transport, and protein homeostasis. We report ALS-causing mutations within the gene encoding the glycosyltransferase GLT8D1. Exome sequencing in an autosomal-dominant ALS pedigree identified p.R92C mutations in GLT8D1, which co-segregate with disease. Sequencing of local and international cohorts demonstrated significant ALS association in the same exon, including additional rare deleterious mutations in conserved amino acids. Mutations are associated with the substrate binding site, and both R92C and G78W changes impair GLT8D1 enzyme activity. Mutated GLT8D1 exhibits in vitro ...


An Exome-Wide Sequencing Study Of The Goldn Cohort Reveals Novel Associations Of Coding Variants And Fasting Plasma Lipids, Xin Geng, Marguerite R. Irvin, Bertha Hidalgo, Stella Aslibekyan, Vinodh Srinivasasainagendra, Ping An, Alexis C. Frazier-Wood, Hemant K. Tiwari, Tushar Dave, Kathleen Ryan, Jose M. Ordovas, Robert J. Straka, Mary F. Feitosa, Paul N. Hopkins, Ingrid Borecki, Michael A. Province, Braxton D. Mitchell, Donna K. Arnett, Degui Zhi Feb 2019

An Exome-Wide Sequencing Study Of The Goldn Cohort Reveals Novel Associations Of Coding Variants And Fasting Plasma Lipids, Xin Geng, Marguerite R. Irvin, Bertha Hidalgo, Stella Aslibekyan, Vinodh Srinivasasainagendra, Ping An, Alexis C. Frazier-Wood, Hemant K. Tiwari, Tushar Dave, Kathleen Ryan, Jose M. Ordovas, Robert J. Straka, Mary F. Feitosa, Paul N. Hopkins, Ingrid Borecki, Michael A. Province, Braxton D. Mitchell, Donna K. Arnett, Degui Zhi

Epidemiology Faculty Publications

Background: Associations of both common and rare genetic variants with fasting blood lipids have been extensively studied. However, most of the rare coding variants associated with lipids are population-specific, and exploration of genetic data from diverse population samples may enhance the identification of novel associations with rare variants.

Results: We searched for novel coding genetic variants associated with fasting lipid levels in 894 samples from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) with exome-wide sequencing-based genotype data. In single variant tests, one variant (rs11171663 in ITGA7) was associated with fasting triglyceride levels (P = 7.66E-08), explaining approximately ...


Hypomorphic Mutations Of Trip11 Cause Odontochondrodysplasia, Anika Wehrle, John A. Follit, Gregory J. Pazour, Andrea Superti-Furga, Martin Lowe, Ekkehart Lausch Feb 2019

Hypomorphic Mutations Of Trip11 Cause Odontochondrodysplasia, Anika Wehrle, John A. Follit, Gregory J. Pazour, Andrea Superti-Furga, Martin Lowe, Ekkehart Lausch

Open Access Articles

Odontochondrodysplasia (ODCD) is an unresolved genetic disorder of skeletal and dental development. Here, we show that ODCD is caused by hypomorphic TRIP11 mutations, and we identify ODCD as the nonlethal counterpart to achondrogenesis 1A (ACG1A), the known null phenotype in humans. TRIP11 encodes Golgi-associated microtubule-binding protein 210 (GMAP-210), an essential tether protein of the Golgi apparatus that physically interacts with intraflagellar transport 20 (IFT20), a component of the ciliary intraflagellar transport complex B. This association and extraskeletal disease manifestations in ODCD point to a cilium-dependent pathogenesis. However, our functional studies in patient-derived primary cells clearly support a Golgi-based disease mechanism ...


Phylogenetic History Of The Amy Gene Cluster In Catarrhines, Christian M. Gagnon Feb 2019

Phylogenetic History Of The Amy Gene Cluster In Catarrhines, Christian M. Gagnon

School of Arts & Sciences Theses

This study phylogenetically analyzed 30 AMY-related genes from 11 primates. The results show the gradual expansion of the AMY gene family which could have allowed primates to adapt to various ecological landscapes and maximize energy intake from starch-rich foods in periods of food scarcity.


A Phewas Study Of A Large Observational Epidemiological Cohort Of African Americans From The Regards Study, Xueyan Zhao, Xin Geng, Vinodh Srinivasasainagendra, Ninad Chaudhary, Suzanne Judd, Virginia Wadley, Orlando M. Gutiérrez, Henry Wang, Ethan M. Lange, Leslie A. Lange, Daniel Woo, Frederick W. Unverzagt, Monika Safford, Mary Cushman, Nita Limdi, Rakale Quarells, Donna K. Arnett, Marguerite R. Irvin, Degui Zhi Jan 2019

A Phewas Study Of A Large Observational Epidemiological Cohort Of African Americans From The Regards Study, Xueyan Zhao, Xin Geng, Vinodh Srinivasasainagendra, Ninad Chaudhary, Suzanne Judd, Virginia Wadley, Orlando M. Gutiérrez, Henry Wang, Ethan M. Lange, Leslie A. Lange, Daniel Woo, Frederick W. Unverzagt, Monika Safford, Mary Cushman, Nita Limdi, Rakale Quarells, Donna K. Arnett, Marguerite R. Irvin, Degui Zhi

Epidemiology Faculty Publications

Background: Cardiovascular disease, diabetes, and kidney disease are among the leading causes of death and disability worldwide. However, knowledge of genetic determinants of those diseases in African Americans remains limited.

Results: In our study, associations between 4956 GWAS catalog reported SNPs and 67 traits were examined among 7726 African Americans from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, which is focused on identifying factors that increase stroke risk. The prevalent and incident phenotypes studied included inflammation, kidney traits, cardiovascular traits and cognition. Our results validated 29 known associations, of which eight associations were reported for the ...


Genome-Wide Characterization, Molecular Evolution And Mexpression Profiling Of The Metacaspases In Potato (Solanum Tuberosum L.), Nehal Dubey, Maitri Trivedi, Suresh Varsani, Vishal Vyas, Manisha Farsodia, Sunil Kumar Singh Jan 2019

Genome-Wide Characterization, Molecular Evolution And Mexpression Profiling Of The Metacaspases In Potato (Solanum Tuberosum L.), Nehal Dubey, Maitri Trivedi, Suresh Varsani, Vishal Vyas, Manisha Farsodia, Sunil Kumar Singh

Faculty Publications: Department of Entomology

Metacaspases are distant relatives of animal caspases found in plants, protozoa and fungi. Some recent studies have demonstrated that metacaspases are involved in regulating the developmental and environmentally induced programmed cell death in plants. In this study, we identified metacaspase gene family in potato (Solanum tuberosum L.) and analyzed their expression pattern in various developmental tissues and stress responses of plants. There were eight metacaspase genes identified in the Peptidase (Cysteine protease) C14 family and based upon sequence alignment and phylogenetic analysis, a systematic nomenclature of potato metacaspases (SotubMCs) has been proposed. Three of the eight candidate genes showing homology ...


The Ethics Of Big Data In Genomics: The Instructive Icelandic Saga Of The Incidentalome, Donna M. Gitter Jan 2019

The Ethics Of Big Data In Genomics: The Instructive Icelandic Saga Of The Incidentalome, Donna M. Gitter

Washington University Global Studies Law Review

DeCODE Genetics, Inc., a pioneering Icelandic biotech firm, recently introduced a free website that permits Icelanders to learn whether they carry mutations in the BRCA2 gene that are known to increase cancer risk, even if these citizens have never participated in genetic testing. Approximately five thousand Icelanders have elected thus far to receive their status. This site is made possible by the consanguinity of Icelandic citizens, who number fewer than 350,000, and their detailed genealogical records dating back centuries, a set of circumstances that presents a unique opportunity to study genetic mutations and the medical disorders associated with them ...


Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna Jan 2019

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks ...