Whole Genome Sequence Data Provides Novel Insights Into the Genetic Architecture of Meat Quality Traits in Beef
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Chapter 7: Monogenic Forms of Diabetes
CHAPTER 7 MONOGENIC FORMS OF DIABETES Mark A. Sperling, MD, and Abhimanyu Garg, MD Dr. Mark A. Sperling is Emeritus Professor and Chair, University of Pittsburgh, Department of Pediatrics, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA. Dr. Abhimanyu Garg is Professor of Internal Medicine and Chief of the Division of Nutrition and Metabolic Diseases at University of Texas Southwestern Medical Center, Dallas, TX. SUMMARY Types 1 and 2 diabetes have multiple and complex genetic influences that interact with environmental triggers, such as viral infections or nutritional excesses, to result in their respective phenotypes: young, lean, and insulin-dependence for type 1 diabetes patients or older, overweight, and often manageable by lifestyle interventions and oral medications for type 2 diabetes patients. A small subset of patients, comprising ~2%–3% of all those diagnosed with diabetes, may have characteristics of either type 1 or type 2 diabetes but have single gene defects that interfere with insulin production, secretion, or action, resulting in clinical diabetes. These types of diabetes are known as MODY, originally defined as maturity-onset diabetes of youth, and severe early-onset forms, such as neonatal diabetes mellitus (NDM). Defects in genes involved in adipocyte development, differentiation, and death pathways cause lipodystrophy syndromes, which are also associated with insulin resistance and diabetes. Although these syndromes are considered rare, more awareness of these disorders and increased availability of genetic testing in clinical and research laboratories, as well as growing use of next generation, whole genome, or exome sequencing for clinically challenging phenotypes, are resulting in increased recognition. A correct diagnosis of MODY, NDM, or lipodystrophy syndromes has profound implications for treatment, genetic counseling, and prognosis. -
NIH Public Access Author Manuscript Pharmacogenomics
NIH Public Access Author Manuscript Pharmacogenomics. Author manuscript; available in PMC 2014 June 12. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Pharmacogenomics. 2014 February ; 15(2): 137–146. doi:10.2217/pgs.13.213. Genome-wide Association and Pharmacological Profiling of 29 Anticancer Agents Using Lymphoblastoid Cell Lines Chad C. Brown1, Tammy M. Havener2, Marisa W. Medina3, John R. Jack1, Ronald M. Krauss3, Howard L. McLeod2, and Alison A. Motsinger-Reif1,2,* 1Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, 27607, USA 2Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA 3Children’s Hospital Oakland Research Institute, Oakland, CA, 94609, USA Abstract Aims—Association mapping with lymphoblastoid cell lines (LCLs) is a promising approach in pharmacogenomics research, and in the current study we utilize this model to perform association mapping for 29 chemotherapy drugs. Materials and Methods—Currently, we use LCLs to perform genome-wide association mapping of the cytotoxic response of 520 European Americans to 29 different anticancer drugs, the largest LCL study to date. A novel association approach using a multivariate analysis of covariance design was employed with the software program MAGWAS, testing for differences in the dose-response profiles between genotypes without making assumptions about the response curve or the biological mode of association. Additionally, by classifying 25 of the 29 drugs into 8 families according to structural and mechanistic relationships, MAGWAS was used to test for associations that were shared across each drug family. -
1 Evidence for Gliadin Antibodies As Causative Agents in Schizophrenia
1 Evidence for gliadin antibodies as causative agents in schizophrenia. C.J.Carter PolygenicPathways, 20 Upper Maze Hill, Saint-Leonard’s on Sea, East Sussex, TN37 0LG [email protected] Tel: 0044 (0)1424 422201 I have no fax Abstract Antibodies to gliadin, a component of gluten, have frequently been reported in schizophrenia patients, and in some cases remission has been noted following the instigation of a gluten free diet. Gliadin is a highly immunogenic protein, and B cell epitopes along its entire immunogenic length are homologous to the products of numerous proteins relevant to schizophrenia (p = 0.012 to 3e-25). These include members of the DISC1 interactome, of glutamate, dopamine and neuregulin signalling networks, and of pathways involved in plasticity, dendritic growth or myelination. Antibodies to gliadin are likely to cross react with these key proteins, as has already been observed with synapsin 1 and calreticulin. Gliadin may thus be a causative agent in schizophrenia, under certain genetic and immunological conditions, producing its effects via antibody mediated knockdown of multiple proteins relevant to the disease process. Because of such homology, an autoimmune response may be sustained by the human antigens that resemble gliadin itself, a scenario supported by many reports of immune activation both in the brain and in lymphocytes in schizophrenia. Gluten free diets and removal of such antibodies may be of therapeutic benefit in certain cases of schizophrenia. 2 Introduction A number of studies from China, Norway, and the USA have reported the presence of gliadin antibodies in schizophrenia 1-5. Gliadin is a component of gluten, intolerance to which is implicated in coeliac disease 6. -
Ccdc80 and Ccdc80-L1: Identification and Functional Analysis of Two Novel Genes Involved in Zebrafish (Danio Rerio) Development
UNIVERSITÀ DEGLI STUDI DI MILANO SCUOLA DI DOTTORATO IN SCIENZE BIOLOGICHE E MOLECOLARI DIPARTIMENTO DI BIOLOGIA DOTTORATO DI RICERCA IN BIOLOGIA CELLULARE E MOLECOLARE XXIV CICLO ccdc80 and ccdc80-l1: Identification and Functional Analysis of Two Novel Genes Involved in Zebrafish (Danio rerio) Development settori scientifico/disciplinari: BIO/06; BIO/11 Tesi di dottorato di Chiara Brusegan R08215 TUTOR: prof. Franco Cotelli COORDINATORE DEL DOTTORATO: prof. Martino Bolognesi A.A. 2010/2011 Index Part I 1. Abstract 1 2. State of the art 2 2.1 Motility of the zebrafish embryo 2 2.2 Muscle formation 3 2.3 Neural differentiation 6 2.4 Identification of zebrafish ccdc80 genes 9 3. Aim of the project 13 4. Materials and Methods 14 4.1 Zebrafish lines and maintenance 14 4.2 Sequence analysis 14 4.3 RT-PCR 15 4.4 Synthesis of probes for whole mount in situ hybridization (WISH) 16 4.5 Whole-mount in situ hybridization 17 4.6 Immunohistochemistry 17 4.7 Histological sections 18 4.8 Injections 18 4.9 Cyclopamine treatment 19 4.10 Statistical analysis 19 5. Results 20 5.1 Identification of ccdc80 homologs in the genome of zebrafish 20 5.2.1 ccdc80 expression profiling 22 5.2.2 ccdc80-loss- and gain-of-function affects somitogenesis in vivo 23 5.2.3 ccdc80 is involved in somitogenesis, but not in the development of the notochord 25 5.2.4 ccdc80 is positively regulated by the Hedgehog pathway 26 5.3.1 ccdc80-l1 expression profiling 27 5.3.2 ccdc80-l1 knocked-down embryos displayed impaired motility 29 5.3.3 ccdc80-l1 loss of function does not affect somitogenesis nor muscle pioneers and adaxial cells formation 30 5.3.4 analysis of neurogenesis of primary motoneurons in ccdc80-l1 morphants 32 5.3.5 Also ccdc80-l1 expression is positively regulated by the Hedgehog pathway 35 5.4.1 ccdc80 expression is not regulated by ccdc80-l1, nor vice versa 37 6. -
Genomic Correlates of Relationship QTL Involved in Fore- Versus Hind Limb Divergence in Mice
Loyola University Chicago Loyola eCommons Biology: Faculty Publications and Other Works Faculty Publications 2013 Genomic Correlates of Relationship QTL Involved in Fore- Versus Hind Limb Divergence in Mice Mihaela Palicev Gunter P. Wagner James P. Noonan Benedikt Hallgrimsson James M. Cheverud Loyola University Chicago, [email protected] Follow this and additional works at: https://ecommons.luc.edu/biology_facpubs Part of the Biology Commons Recommended Citation Palicev, M, GP Wagner, JP Noonan, B Hallgrimsson, and JM Cheverud. "Genomic Correlates of Relationship QTL Involved in Fore- Versus Hind Limb Divergence in Mice." Genome Biology and Evolution 5(10), 2013. This Article is brought to you for free and open access by the Faculty Publications at Loyola eCommons. It has been accepted for inclusion in Biology: Faculty Publications and Other Works by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. © Palicev et al., 2013. GBE Genomic Correlates of Relationship QTL Involved in Fore- versus Hind Limb Divergence in Mice Mihaela Pavlicev1,2,*, Gu¨ nter P. Wagner3, James P. Noonan4, Benedikt Hallgrı´msson5,and James M. Cheverud6 1Konrad Lorenz Institute for Evolution and Cognition Research, Altenberg, Austria 2Department of Pediatrics, Cincinnati Children‘s Hospital Medical Center, Cincinnati, Ohio 3Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University 4Department of Genetics, Yale University School of Medicine 5Department of Cell Biology and Anatomy, The McCaig Institute for Bone and Joint Health and the Alberta Children’s Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Canada 6Department of Anatomy and Neurobiology, Washington University *Corresponding author: E-mail: [email protected]. -
Transcriptional Regulation of RKIP in Prostate Cancer Progression
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Sciences Transcriptional Regulation of RKIP in Prostate Cancer Progression Submitted by: Sandra Marie Beach In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Sciences Examination Committee Major Advisor: Kam Yeung, Ph.D. Academic William Maltese, Ph.D. Advisory Committee: Sonia Najjar, Ph.D. Han-Fei Ding, M.D., Ph.D. Manohar Ratnam, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: May 16, 2007 Transcriptional Regulation of RKIP in Prostate Cancer Progression Sandra Beach University of Toledo ACKNOWLDEGMENTS I thank my major advisor, Dr. Kam Yeung, for the opportunity to pursue my degree in his laboratory. I am also indebted to my advisory committee members past and present, Drs. Sonia Najjar, Han-Fei Ding, Manohar Ratnam, James Trempe, and Douglas Pittman for generously and judiciously guiding my studies and sharing reagents and equipment. I owe extended thanks to Dr. William Maltese as a committee member and chairman of my department for supporting my degree progress. The entire Department of Biochemistry and Cancer Biology has been most kind and helpful to me. Drs. Roy Collaco and Hong-Juan Cui have shared their excellent technical and practical advice with me throughout my studies. I thank members of the Yeung laboratory, Dr. Sungdae Park, Hui Hui Tang, Miranda Yeung for their support and collegiality. The data mining studies herein would not have been possible without the helpful advice of Dr. Robert Trumbly. I am also grateful for the exceptional assistance and shared microarray data of Dr. -
Abstracts from the 9Th Biennial Scientific Meeting of The
International Journal of Pediatric Endocrinology 2017, 2017(Suppl 1):15 DOI 10.1186/s13633-017-0054-x MEETING ABSTRACTS Open Access Abstracts from the 9th Biennial Scientific Meeting of the Asia Pacific Paediatric Endocrine Society (APPES) and the 50th Annual Meeting of the Japanese Society for Pediatric Endocrinology (JSPE) Tokyo, Japan. 17-20 November 2016 Published: 28 Dec 2017 PS1 Heritable forms of primary bone fragility in children typically lead to Fat fate and disease - from science to global policy a clinical diagnosis of either osteogenesis imperfecta (OI) or juvenile Peter Gluckman osteoporosis (JO). OI is usually caused by dominant mutations affect- Office of Chief Science Advsor to the Prime Minister ing one of the two genes that code for two collagen type I, but a re- International Journal of Pediatric Endocrinology 2017, 2017(Suppl 1):PS1 cessive form of OI is present in 5-10% of individuals with a clinical diagnosis of OI. Most of the involved genes code for proteins that Attempts to deal with the obesity epidemic based solely on adult be- play a role in the processing of collagen type I protein (BMP1, havioural change have been rather disappointing. Indeed the evidence CREB3L1, CRTAP, LEPRE1, P4HB, PPIB, FKBP10, PLOD2, SERPINF1, that biological, developmental and contextual factors are operating SERPINH1, SEC24D, SPARC, from the earliest stages in development and indeed across generations TMEM38B), or interfere with osteoblast function (SP7, WNT1). Specific is compelling. The marked individual differences in the sensitivity to the phenotypes are caused by mutations in SERPINF1 (recessive OI type obesogenic environment need to be understood at both the individual VI), P4HB (Cole-Carpenter syndrome) and SEC24D (‘Cole-Carpenter and population level. -
Cyclin K Interacts with Β-Catenin to Induce Cyclin D1 Expression And
Theranostics 2020, Vol. 10, Issue 24 11144 Ivyspring International Publisher Theranostics 2020; 10(24): 11144-11158. doi: 10.7150/thno.42578 Research Paper Cyclin K interacts with β-catenin to induce Cyclin D1 expression and facilitates tumorigenesis and radioresistance in lung cancer Guojun Yao*, Jing Tang*, Xijie Yang, Ye Zhao, Rui Zhou, Rui Meng, Sheng Zhang, Xiaorong Dong, Tao Zhang, Kunyu Yang, Gang Wu and Shuangbing Xu Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. *These authors contributed equally to this work. Corresponding author: Shuangbing Xu or Gang Wu, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. E-mail: [email protected] or [email protected]. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. Received: 2019.11.29; Accepted: 2020.08.24; Published: 2020.09.11 Abstract Rationale: Radioresistance remains the major cause of local relapse and distant metastasis in lung cancer. However, the underlying molecular mechanisms remain poorly defined. This study aimed to investigate the role and regulatory mechanism of Cyclin K in lung cancer radioresistance. Methods: Expression levels of Cyclin K were measured by immunohistochemistry in human lung cancer tissues and adjacent normal lung tissues. Cell growth and proliferation, neutral comet and foci formation assays, G2/M checkpoint and a xenograft mouse model were used for functional analyses. Gene expression was examined by RNA sequencing and quantitative real-time PCR. -
Effects of Activation of the LINE-1 Antisense Promoter on the Growth of Cultured Cells
www.nature.com/scientificreports OPEN Efects of activation of the LINE‑1 antisense promoter on the growth of cultured cells Tomoyuki Honda1*, Yuki Nishikawa1, Kensuke Nishimura1, Da Teng1, Keiko Takemoto2 & Keiji Ueda1 Long interspersed element 1 (LINE‑1, or L1) is a retrotransposon that constitutes ~ 17% of the human genome. Although ~ 6000 full‑length L1s spread throughout the human genome, their biological signifcance remains undetermined. The L1 5′ untranslated region has bidirectional promoter activity with a sense promoter driving L1 mRNA production and an antisense promoter (ASP) driving the production of L1‑gene chimeric RNAs. Here, we stimulated L1 ASP activity using CRISPR‑Cas9 technology to evaluate its biological impacts. Activation of the L1 ASP upregulated the expression of L1 ASP‑driven ORF0 and enhanced cell growth. Furthermore, the exogenous expression of ORF0 also enhanced cell growth. These results indicate that activation of L1 ASP activity fuels cell growth at least through ORF0 expression. To our knowledge, this is the frst report demonstrating the role of the L1 ASP in a biological context. Considering that L1 sequences are desilenced in various tumor cells, our results indicate that activation of the L1 ASP may be a cause of tumor growth; therefore, interfering with L1 ASP activity may be a potential strategy to suppress the growth. Te human genome contains many transposable element-derived sequences, such as endogenous retroviruses and long interspersed element 1 (LINE-1, or L1). L1 is one of the major classes of retrotransposons, and it constitutes ~ 17% of the human genome1. Full-length L1 consists of a 5′ untranslated region (UTR), two open reading frames (ORFs) that encode the proteins ORF1p and ORF2p, and a 3′ UTR with a polyadenylation signal. -
4-6 Weeks Old Female C57BL/6 Mice Obtained from Jackson Labs Were Used for Cell Isolation
Methods Mice: 4-6 weeks old female C57BL/6 mice obtained from Jackson labs were used for cell isolation. Female Foxp3-IRES-GFP reporter mice (1), backcrossed to B6/C57 background for 10 generations, were used for the isolation of naïve CD4 and naïve CD8 cells for the RNAseq experiments. The mice were housed in pathogen-free animal facility in the La Jolla Institute for Allergy and Immunology and were used according to protocols approved by the Institutional Animal Care and use Committee. Preparation of cells: Subsets of thymocytes were isolated by cell sorting as previously described (2), after cell surface staining using CD4 (GK1.5), CD8 (53-6.7), CD3ε (145- 2C11), CD24 (M1/69) (all from Biolegend). DP cells: CD4+CD8 int/hi; CD4 SP cells: CD4CD3 hi, CD24 int/lo; CD8 SP cells: CD8 int/hi CD4 CD3 hi, CD24 int/lo (Fig S2). Peripheral subsets were isolated after pooling spleen and lymph nodes. T cells were enriched by negative isolation using Dynabeads (Dynabeads untouched mouse T cells, 11413D, Invitrogen). After surface staining for CD4 (GK1.5), CD8 (53-6.7), CD62L (MEL-14), CD25 (PC61) and CD44 (IM7), naïve CD4+CD62L hiCD25-CD44lo and naïve CD8+CD62L hiCD25-CD44lo were obtained by sorting (BD FACS Aria). Additionally, for the RNAseq experiments, CD4 and CD8 naïve cells were isolated by sorting T cells from the Foxp3- IRES-GFP mice: CD4+CD62LhiCD25–CD44lo GFP(FOXP3)– and CD8+CD62LhiCD25– CD44lo GFP(FOXP3)– (antibodies were from Biolegend). In some cases, naïve CD4 cells were cultured in vitro under Th1 or Th2 polarizing conditions (3, 4). -
(12) United States Patent (10) Patent No.: US 9,309,565 B2 Kelly Li, San
US0093 09565B2 (12) United States Patent (10) Patent No.: US 9,309,565 B2 BrOOmer et al. (45) Date of Patent: Apr. 12, 2016 (54) KARYOTYPING ASSAY 4,889,818. A 12/1989 Gelfand et al. 4,965,188 A 10, 1990 Mullis et al. (75) Inventors: Adam Broomer, Carlsbad, CA (US); 5.835 A RE E. tal Kelly Li, San Jose, CA (US), Andreas 3.66: A 56, RI. R. Tobler, Fremont, CA (US); Caifu 5.436,134. A 7/1995 Haugland et al. Chen, Palo Alto, CA (US); David N. 5,487.972 A 1/1996 Gelfand et al. Keys, Jr., Oakland, CA (US) 5,538,848. A 7/1996 Livak et al. s s 5,618,711 A 4/1997 Gelfand et al. (73) Assignee: Life Technologies Corporation, 5,677,1525,658,751 A 10/19978, 1997 Yues et. al. al. Carlsbad, CA (US) 5,723,591 A 3/1998 Livak et al. 5,773.258 A 6/1998 Birch et al. (*) Notice: Subject to any disclaimer, the term of this 5,789,224 A 8, 1998 Gelfand et al. patent is extended or adjusted under 35 38. A 3. 3. E. al U.S.C. 154(b) by 998 days. 5,854,033.sy w A 12/1998 LizardiCaO (ca. 5,876,930 A 3, 1999 Livak et al. (21) Appl. No.: 13/107,786 5,994,056. A 1 1/1999 Higuchi (22) Filed: May 13, 2011 (Continued) (65) Prior Publication Data FOREIGN PATENT DOCUMENTS US 2011 FO281755A1 Nov. 17, 2011 EP OOTO685 A2 1, 1983 WO WO-2006/081222 8, 2006 Related U.S. -
Integrating Single-Step GWAS and Bipartite Networks Reconstruction Provides Novel Insights Into Yearling Weight and Carcass Traits in Hanwoo Beef Cattle
animals Article Integrating Single-Step GWAS and Bipartite Networks Reconstruction Provides Novel Insights into Yearling Weight and Carcass Traits in Hanwoo Beef Cattle Masoumeh Naserkheil 1 , Abolfazl Bahrami 1 , Deukhwan Lee 2,* and Hossein Mehrban 3 1 Department of Animal Science, University College of Agriculture and Natural Resources, University of Tehran, Karaj 77871-31587, Iran; [email protected] (M.N.); [email protected] (A.B.) 2 Department of Animal Life and Environment Sciences, Hankyong National University, Jungang-ro 327, Anseong-si, Gyeonggi-do 17579, Korea 3 Department of Animal Science, Shahrekord University, Shahrekord 88186-34141, Iran; [email protected] * Correspondence: [email protected]; Tel.: +82-31-670-5091 Received: 25 August 2020; Accepted: 6 October 2020; Published: 9 October 2020 Simple Summary: Hanwoo is an indigenous cattle breed in Korea and popular for meat production owing to its rapid growth and high-quality meat. Its yearling weight and carcass traits (backfat thickness, carcass weight, eye muscle area, and marbling score) are economically important for the selection of young and proven bulls. In recent decades, the advent of high throughput genotyping technologies has made it possible to perform genome-wide association studies (GWAS) for the detection of genomic regions associated with traits of economic interest in different species. In this study, we conducted a weighted single-step genome-wide association study which combines all genotypes, phenotypes and pedigree data in one step (ssGBLUP). It allows for the use of all SNPs simultaneously along with all phenotypes from genotyped and ungenotyped animals. Our results revealed 33 relevant genomic regions related to the traits of interest.