Lesson 3: Genetics
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AMP Molecular Genetic Pathology Recommended Review Books
ASSOCIATION FOR MOLECULAR PATHOLOGY Education. Innovation & Improved Patient Care. Advocacy. 6120 Executive Blvd. Suite 700, Rockville, MD 20852 Tel: 301-634-7939 | Fax: 301-634-7995 | [email protected] | www.amp.org AMP Molecular Genetic Pathology : RECOMMENDED REVIEW BOOKS Updated: March, 2021 The following books are suggested for those preparing for the Molecular Genetic Pathology board exam administered by the American Board of Medical Genetics and the American Board of Pathology. This list represents the recommendations of the MGP Review Course faculty and the AMP Training and Education Committee; endorsement by the ABMG or the ABP is not implied. GENERAL MOLECULAR PATHOLOGY Thompson & Thompson Genetics in Medicine, 8th edition Nussbaum RL et al., eds. Elsevier, 2015 Molecular Pathology: The Molecular Basis of Human Diseases 2nd edition Coleman WB and Tsongalis GJ, eds. Elsevier, 2018 Diagnostic Molecular Pathology: A Guide to Applied Molecular Testing Coleman WB and Tsongalis GJ, eds. Elsevier, 2016 Molecular Basis of Human Cancer, 2nd edition Coleman WB and Tsongalis GJ, eds. Elsevier, 2017 Molecular Diagnostics: Fundamentals, Methods, and Clinical Applications 3rd edition Buckingham L. ASCP, 2021 Genomic Medicine: A Practical Guide Tafe LJ and Arcila ME, eds. Springer, 2020 CYTOGENETICS Gardner and Sutherland’s Chromosome Abnormalities and Genetic Counseling, 5th edition McKinlay Gardner RJ, Amor DJ. Oxford University Press, 2018 The Principles of Clinical Cytogenetics, 3rd edition Gersen SL and Keagle MB, eds. Human Press, 2013 Human Chromosomes, 4th edition Miller OJ and Therman E, eds. Springer Press, 2000 Vance GH, Khan WA. Utility of Fluorescence In Situ Hybridization in Clinical and Research Applications. Advances in Molecular Pathology 2020; 3:65-75. -
Bio 102 Practice Problems Genetic Code and Mutation
Bio 102 Practice Problems Genetic Code and Mutation Multiple choice: Unless otherwise directed, circle the one best answer: 1. Choose the one best answer: Beadle and Tatum mutagenized Neurospora to find strains that required arginine to live. Based on the classification of their mutants, they concluded that: A. one gene corresponds to one protein. B. DNA is the genetic material. C. "inborn errors of metabolism" were responsible for many diseases. D. DNA replication is semi-conservative. E. protein cannot be the genetic material. 2. Choose the one best answer. Which one of the following is NOT part of the definition of a gene? A. A physical unit of heredity B. Encodes a protein C. Segement of a chromosome D. Responsible for an inherited characteristic E. May be linked to other genes 3. A mutation converts an AGA codon to a TGA codon (in DNA). This mutation is a: A. Termination mutation B. Missense mutation C. Frameshift mutation D. Nonsense mutation E. Non-coding mutation 4. Beadle and Tatum performed a series of complex experiments that led to the idea that one gene encodes one enzyme. Which one of the following statements does not describe their experiments? A. They deduced the metabolic pathway for the synthesis of an amino acid. B. Many different auxotrophic mutants of Neurospora were isolated. C. Cells unable to make arginine cannot survive on minimal media. D. Some mutant cells could survive on minimal media if they were provided with citrulline or ornithine. E. Homogentisic acid accumulates and is excreted in the urine of diseased individuals. 5. -
Coincident Two Mutations and One Single Nucleotide Polymorphism of the PTCH1 Gene in a Family with Naevoid Basal Cell Carcinoma Syndrome
Letters to the Editor 635 Coincident Two Mutations and One Single Nucleotide Polymorphism of the PTCH1 Gene in a Family with Naevoid Basal Cell Carcinoma Syndrome Shoko Abe1, Kenji Kabashima1*, Jun-ichi Sakabe1, Takatoshi Shimauchi1, Zhang Yan2, Tetsuji Okamoto2 and Yoshiki Tokura1 1Department of Dermatology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, and 2Department of Molecular Oral Medicine and Maxillofacial Surgery 1, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. E-mail: [email protected] Accepted May 7, 2008. Sir, at nucleotide position 667 within exon 3 and an intervening se- Naevoid basal cell carcinoma syndrome (NBCCS, OMIM quence (IVS)16 -3T > C, and a SNP; IVS10 -8T > C, were detected in all three cases. A deletion of AGAC causes a frameshift and a #109400), also called Gorlin’s syndrome, is an autosomal subsequent stop codon in exon 3, which prematurely truncates dominant disease that affects about 1 in 60,000 indivi- the protein (Fig. 1a). In addition, the IVS16 -3T > C could lead duals (1, 2). NBCCS is associated with various skeletal to an aberrant splicing and truncation of PTCH1 (10–12). and neurocutaneous abnormalities. Major manifestations To detect the expression level of PTCH1 protein in the skin, are multiple basal cell carcinomas (BCCs), odontogenic an immunohistochemical study was performed using goat poly- clonal anti-PTCH1 antibody (G-19; Santa Cruz Biotechnology, keratocysts, palmoplantar dyskeratotic pits and intra- Santa Cruz, CA, USA). Enzyme reactions were developed with cranial calcification (3). In addition, rib and vertebral conventional substrates for diamino-benzidine (Sigma, St Louis, malformations, epidermal cysts, macrocephaly, facial MO, USA) (13). -
Antibiotic Resistance by High-Level Intrinsic Suppression of a Frameshift Mutation in an Essential Gene
Antibiotic resistance by high-level intrinsic suppression of a frameshift mutation in an essential gene Douglas L. Husebya, Gerrit Brandisa, Lisa Praski Alzrigata, and Diarmaid Hughesa,1 aDepartment of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala SE-751 23, Sweden Edited by Sankar Adhya, National Institutes of Health, National Cancer Institute, Bethesda, MD, and approved January 4, 2020 (received for review November 5, 2019) A fundamental feature of life is that ribosomes read the genetic (unlikely if the DNA sequence analysis was done properly), that the code in messenger RNA (mRNA) as triplets of nucleotides in a mutants carry frameshift suppressor mutations (15–17), or that the single reading frame. Mutations that shift the reading frame gen- mRNA contains sequence elements that promote a high level of ri- erally cause gene inactivation and in essential genes cause loss of bosomal shifting into the correct reading frame to support cell viability viability. Here we report and characterize a +1-nt frameshift mutation, (10). Interest in understanding these mutations goes beyond Mtb and centrally located in rpoB, an essential gene encoding the beta-subunit concerns more generally the potential for rescue of mutants that ac- of RNA polymerase. Mutant Escherichia coli carrying this mutation are quire a frameshift mutation in any essential gene. We addressed this viable and highly resistant to rifampicin. Genetic and proteomic exper- by isolating a mutant of Escherichia coli carrying a frameshift mutation iments reveal a very high rate (5%) of spontaneous frameshift suppres- in rpoB and experimentally dissecting its genotype and phenotypes. sion occurring on a heptanucleotide sequence downstream of the mutation. -
Leave Policy for Residents and Fellows.Pdf
Leave Policy for Residents and Fellows The following policy outlines indications and training modifications to accommodate leave during accredited training for certification in all of the ABMGG specialties. Candidates for certification are required to successfully complete training in one of the following programs: ACGME-accredited Programs: 24 months (2 years) • Medical Genetics and Genomics Residency • Clinical Biochemical Genetics Postdoctoral Fellowship • Laboratory Genetics and Genomics Postdoctoral Fellowship Approved Combined Residency Programs: 48 months (4 years) • Medical Genetics and Genomics/Internal Medicine • Medical Genetics and Genomics/Pediatrics • Medical Genetics and Genomics/Maternal Fetal Medicine • Medical Genetics and Genomics/Reproductive Endocrinology and Infertility Subspecialty Fellowship Programs: 12 months (1 year) • Medical Biochemical Genetics • Molecular Genetic Pathology (cosponsored with American Board of Pathology) General Leave Policy: All candidates are allotted 4 weeks leave per year, which may be accrued or averaged through the duration of training for any indication. All candidates must take at least one week off per year as designated vacation time. Leave time cannot be forfeited to shorten training duration. Parental, Caregiver, and Medical Leave Policy: This policy refers to leave for the following indications: parental leave (the birth and care of a newborn including adopted and foster children for either partner), caregiver leave (care for an immediate (first degree) family member or partner with a serious health condition), or medical leave for significant personal medical needs. For Parental, Caregiver, and Medical leave, the ABMGG will allow up to 6 weeks leave during an academic year to occur once during the training program. For trainees who take indicated leave, they must still take at least one additional week for vacation during the same training year. -
Why Are Frameshift Homologs Widespread Within and Across Species?
bioRxiv preprint doi: https://doi.org/10.1101/067736; this version posted August 25, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The shiftability of the protein coding genes 1 Why are frameshift homologs widespread within and across species? 2 Xiaolong Wang*1, Quanjiang Dong2, Gang Chen1, Jianye Zhang1, Yongqiang Liu1, Jinqiao 3 Zhao1, Haibo Peng1, Yalei Wang1, Yujia Cai1, Xuxiang Wang1, Chao Yang1 4 1. College of Life Sciences, Ocean University of China, Qingdao, 266003, P. R. China 5 2. Qingdao Municipal Hospital, Qingdao, Shandong, 266003, P. R. China 6 Abstract 7 Frameshifted coding genes presumably yield truncated and dysfunctional proteins. 8 We report that frameshift homologs, including frameshift orthologs and frameshift 9 paralogs, are actually widespread within and across species. We proposed that protein 10 coding genes have a ca-0.5 quasi-constant shiftability: given any protein coding 11 sequence, at least 50% of the amino acids remain conserved in a frameshifted protein 12 sequence. In the natural genetic code, amino acid pairs assigned to frameshift codon 13 substitutions are more conserved than those to random codon substitutions, and the 14 frameshift tolerating ability of the natural genetic code ranks among the best 6% of all 15 compatible genetic codes. Hence, the shiftability of protein coding genes was mainly 16 predefined by the standard genetic code, while additional sequence-level shiftability 17 was achieved through biased usages of codons and codon pairs. We concluded that 18 during early evolution the genetic code was symmetrically optimized for tolerate 19 frameshifts, so that protein coding genes were endowed an inherent ability to tolerate 20 frameshifting in both forward and backward directions. -
Department of Molecular Biology and Immunology
Genetics Student Handbook 2020-2021 The information provided in this document serves to supplement the requirements of the Graduate School of Biomedical Sciences detailed in the UNTHSC Catalog with requirements specific to the Genetics discipline. Genetics Discipline (8/6/20) 1 Table of Contents Page Description of the Genetics Discipline ............................................ 3 Graduate Faculty and Their Research ............................................. 5 Requirements ................................................................................... 9 Required Courses ....................................................................... 9 Journal Club and Seminar Courses ............................................ 9 Elective Courses ......................................................................... 9 Sample Degree Plans ..................................................................... 11 Advancement to Candidacy ........................................................... 14 Genetics Discipline (8/6/20) 2 1. Description of the Genetics Discipline John V. Planz, Ph.D., Graduate Advisor Center for BioHealth, Rm 360 Phone: 817-735-2397 E-mail: [email protected] Program website: www.unthsc.edu/graduate-school-of-biomedical-sciences/genetics/ Graduate Faculty: Allen; Barber; Budowle; Cihlar; Coble; Ge; Phillips; Planz; Woerner Genetics is a broad interdisciplinary field that unites biochemistry, microbial and cellular biology, molecular processes, biotechnology, computational biology, biogeography and human disease -
Point Mutations Underlying NF1 and NF2 and Increased Risk of Malignancy
Central Annals of Otolaryngology and Rhinology Mini Review *Corresponding author Andrea L.O. Hebb, MSc, PhD, RN, Maritime Lateral Skull Base Clinic, Otolaryngology, Neurosurgery and the Point Mutations Underlying NF1 Stereotactic Radiotherapy Group QEII Health Science Centre, Halifax, Canada; Email: [email protected] and NF2 and Increased Risk of Submitted: 12 February 2020 Accepted: 25 February 2020 Published: 27 February 2020 Malignancy ISSN: 2379-948X Copyright 1 2 3,4 3,4 Myles Davidson , Haupt TS , Morris DP , Shoman NM , © 2020 Davidson M, et al. 2,4 1,2,4 Walling SA , and Hebb ALO * OPEN ACCESS 1Department of Psychology, Saint Mary’s University, Canada 2Division of Neurosurgery, Dalhousie University, Canada Keywords 3 Division of Otolaryngology, Dalhousie University, Canada • Neurofibromatosis 4 Maritime Lateral Skull Base Clinic, Otolaryngology, Neurosurgery and the Stereotactic • Missense mutation Radiotherapy Group QEII Health Science Centre, Canada • Frameshift mutation • Nonsense mutation Abstract • KRAS gene • Colorectal cancer Neurofibromatosis Type-1 and Neurofibromatosis Type-2 are autosomal dominant • Acoustic neuroma tumor suppressor disorders that result from inherited or spontaneous mutations in • Vestibular schwannoma their respective genes. Neurofibromatosis Type-1 has been attributed to a non-sense • Meningioma mutation in chromosome 17 and Neurofibromatosis Type-2 a point mutation in its gene on chromosome 22. The following discussion briefly reviews point and frameshift mutations and explores the relationship between point mutations and development of malignancies in patients with Neurofibromatosis Type-1 and Neurofibromatosis Type-2. INTRODUCTION producing phenylalanine hydroxylase, the majority of which are missense mutations [4]. A point mutation is the change of one base for another in the DNA sequence. -
Importance of Medical Genetics Research in Medicine
cs an eti d D n N e A G f R Journal of Genetics and DNA o e l s a e a n Sboui S, Tabbabi A, J Genet DNA Res 2018, 2:1 r r c u h o J Research Short Communication Open Access Importance of Medical Genetics Research in Medicine Sajida Sboui1 and Ahmed Tabbabi2* 1Faculty of Medicine of Monastir, Monastir University, Monastir, Tunisia 2Department of Hygiene and Environmental Protection, Ministry of Public Health, Tunis, Tunisia *Corresponding author: Ahmed Tabbabi, Department of Hygiene and Environmental Protection, Ministry of Public Health, Tunis, Tunisia, Tel: +216 71 577 115; +216 71 577 302; E-mail: [email protected] Received date: February 09, 2018, Accepted date: February 20, 2018, Published date: February 27, 2018 Copyright: © 2018 Sboui S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Keywords: Chromosome; Genes; Cleft lip; Transforming growth In medical genetics, the work diagnosis includes molecular analyzes factors (DNA, proteins and chromosomes) and clinical manisfestations of conditions, including malformations birth. If monogenic diseases are Short Communication rare, those caused by the gene/environment interaction are common and include many diseases. Prevention in medical genetics involves for About millions of families are affected by hereditary diseases around common pathologies the identification of subjects with high risk, with the world. Statistics analysis showed that about 5% of all pregnancies the intention of preventing the disease (e.g. -
An Updated Primer
The new england journal of medicine review article Genomic Medicine W. Gregory Feero, M.D., Ph.D., and Alan E. Guttmacher, M.D., Editors Genomic Medicine — An Updated Primer W. Gregory Feero, M.D., Ph.D., Alan E. Guttmacher, M.D., and Francis S. Collins, M.D., Ph.D. Cathy, a 40-year-old mother of three, arrives in your office for her annual physical. From the National Human Genome Re- She has purchased a commercial genomewide scan (see the Glossary), which she be- search Institute (W.G.F.), the Eunice Ken- nedy Shriver National Institute of Child lieves measures the clinically meaningful risk that common diseases will develop, H e al t h an d Human D e ve l o p m e n t ( A . E .G .), and has completed her family history online using My Family Health Portrait (www and the Office of the Director (F.S.C.), .familyhistory.hhs.gov), a tool developed for this purpose by the U.S. Surgeon Gen- National Institutes of Health, Bethesda, MD; and the Maine Dartmouth Family eral. Her genomewide scan suggests a slightly elevated risk of breast cancer, but Medicine Residency Program, Augusta, you correctly recognize that this information is of unproven value in routine clinical ME (W.G.F.). Address reprint requests to care. On importing Cathy’s family-history file, your office’s electronic health record Dr. Feero at the National Human Ge- nome Research Institute, National Insti- system alerts you to the fact that Cathy is of Ashkenazi Jewish heritage and has sev- tutes of Health, Bldg. -
Genetic Testing for BRCA Mutations: a POLICY PAPER
Genetic testing for BRCA mutations: A POLICY PAPER 2019 This report was initiated and funded by Pfizer. Pfizer has provided funding to The Health Policy Partnership (HPP) for research, drafting and coordination. The report was written by Kirsten Budig, Jody Tate and Suzanne Wait from HPP under the guidance of a group of expert contributors. The experts contributed through telephone interviews and written comments, and were not financially compensated for their time. The following expert contributors were consulted and provided feedback during the development of this European-level report and the country profiles, for which we are hugely grateful. European-level report • Karen Benn, Deputy CEO/ Head of Public Affairs, Europa Donna • Antonella Cardone, Director, European Cancer Patient Coalition • Lydia Makaroff, former Director, European Cancer Patient Coalition; current Chief Executive Officer, Fight Bladder Cancer • Elżbieta Senkus-Konefka, Associate Professor at the Department of Oncology and Radiotherapy, Medical University of Gdańsk, Poland France country profile • Pascal Pujol, President, BRCA-France; Professor of Medical Genetics, Centre Hospitalier Universitaire de Montpellier • Dominique Stoppa-Lyonnet, Director of the Genetics Department, Institut Curie; Professor of Genetics, University Paris-Descartes Germany country profile • Rita Schmutzler, Director, Centre for Breast and Ovarian Cancer, Cologne • Evelin Schröck, Director, Institute for Clinical Genetics at the TU Dresden Ireland country profile • Liz Yeates, CEO, Marie -
Genomic-Based Personalized Medicine (Reference Committee E)
REPORT 4 OF THE COUNCIL ON SCIENCE AND PUBLIC HEALTH (A-10) Genomic-based Personalized Medicine (Reference Committee E) EXECUTIVE SUMMARY Objectives. The term “personalized medicine” (PM) refers to health care that is informed by each person’s unique clinical, genetic, and environmental information. Clinical integration of PM technologies is enabling health care providers to more easily detect individual differences in susceptibility to particular diseases or in response to specific treatments, then tailor preventive and therapeutic interventions to maximize benefit and minimize harm. This report will review current status of genomic-based PM and challenges to implementing it, and will briefly summarize the activities of key federal agencies, professional organizations, coalitions, and health systems that are working to further the integration of genomic-based technologies into routine care. Data Sources. Literature searches were conducted in the PubMed database for English-language articles published between 2005 and 2010 using the search terms “personalized medicine” and “personalized medicine AND clinic.” To capture reports that may not have been indexed on PubMed, a Google search was also conducted using the search term “personalized medicine.” Additional articles were identified by review of the literature citations in articles and identified from the PubMed and Google searches. Results. Genetic testing has been a routine part of clinical care for a number of years in screening and diagnosis. Recently, a number of genomic-based applications have advanced beyond these screening and diagnostic techniques and are “personalizing” the delivery of care by enabling risk prediction, therapy, and prognosis that is tailored to individual patients. Yet there are challenges to the clinical implementation of PM, such as the lack of genetics knowledge among health care providers, slow generation of clinical validity and utility evidence, a fragmentary oversight and regulatory system, and lack of insurance coverage of PM technologies.