Medical Genetics & Genomics Guri Tzivion, PhD BCHM 590: Winter 2016 Windsor University School of Medicine

Dr. Guri Tzivion  PhD, Immunology and Microbiology, the Hebrew University, Jerusalem, Israel  Postdoc, Molecular Cancer Biology, Harvard Medical School, Boston, MA  Assistant Professor, Texas A&M Medical School  Associate Professor, Karmanos Cancer Center & Pathology, Wayne State University, Detroit, MI  Associate Professor, Cancer Institute & Biochemistry, University of Mississippi Medical School, Jackson, MS

Dr. Guri Tzivion Dr. Guri Tzivion  Research Interests: Mechanisms of signal transduction involved in cancer pathogenesis, specifically the Ras-Raf-MAPK pathway and the PI3K-AKT pathway. Modulators of the Nicotinamide-sirtuin pathway as potential therapeutic agents in metabolic disorders and aging.

Definitions Genetics: The study of specific, individual genes and their role in inheritance. (In medicine, genetics has historically applied to the study of rare single gene disorders). Genetics: The study of specific, individual genes and their role in inheritance. (In medicine, genetics has historically applied to the study of rare single gene disorders). Genomics: The study of an organism's entire genetic makeup (genome)and its interaction with environmental or non-genetic factors, including lifestyle. Genomics: The study of an organism's entire genetic makeup (genome)and its interaction with environmental or non-genetic factors, including lifestyle. – Applied to the study of complex diseases such as cancer, diabetes, heart disease, hypertension and asthma.

Definitions Genomic Medicine: The medical discipline that involves using genomic information about an individual as part of his/her comprehensive health care supervision (e.g., for diagnostic or therapeutic decision-making). Genomic Medicine: The medical discipline that involves using genomic information about an individual as part of his/her comprehensive health care supervision (e.g., for diagnostic or therapeutic decision-making). − Genomic medicine is becoming an integral part of primary care for adults.

Why Must Primary Care Physicians Understand Genetics and Genomics? To answer requests for information To answer requests for information – Practitioners need to be able to respond to patients' questions about the possibility of a genetic disease in the family. – A survey conducted by the American Medical Association in March 1998 found that 71% of patients who questioned whether there was a genetic disease in their family would contact their primary care physician first. American Medical Association. Genetic testing: a study of consumer attitudes. March 1998: AMA survey results. Accessed September 23, 2007.

Why Must Primary Care Physicians Understand Genetics and Genomics? To assist in case recognition To assist in case recognition – By increasing their awareness of the manifestations of common genetic diseases, practitioners can expand the differential diagnoses of some patients' symptoms to include common genetic diseases. – Whereas all diseases have both a genetic and an environmental component, in some, the genetic effect predominates, and these are commonly referred to as “genetic diseases.”

Why Must Primary Care Physicians Understand Genetics and Genomics? To provide effective health supervision for patients with genetic disorders To provide effective health supervision for patients with genetic disorders – Practitioners need to know how patients' primary genetic diseases may affect their health, what secondary diseases they are likely to develop, and the unusual ways that common diseases may present in these patients. Children and adolescents with genetic disorders must transition to knowledgeable adult primary care physicians who can provide comprehensive health supervision. Children and adolescents with genetic disorders must transition to knowledgeable adult primary care physicians who can provide comprehensive health supervision.

Why Must Primary Care Physicians Understand Genetics and Genomics? To screen for potential genetic disorders in patients in their practices To screen for potential genetic disorders in patients in their practices – Genetic screening measures historically have focused on reproductive issues, such as preconception screening for those at risk of being carriers of autosomal recessive diseases (Tay-Sachs disease, CF) or prenatal diagnosis (Down syndrome). – Newborn screening is generally mandated by state or federal government health policies and occurs outside the physician's purview (newborn screening).

Why Must Primary Care Physicians Understand Genetics and Genomics? – The role of genetics and genomics in routine health care maintenance for adults as a means to assess the genetic risk of disease is becoming increasingly important. An understanding of the genomic components of the common chronic diseases of adult life will lead to a personalized approach to health supervision, i.e, personalized or genomic medicine. An understanding of the genomic components of the common chronic diseases of adult life will lead to a personalized approach to health supervision, i.e, personalized or genomic medicine.

Genomic Medicine Future State In addition to the usual tools physicians use in health assessment, the tools of genomics will allow for personalizing: – Screening protocols for heart disease, cancer and other chronic disorders – Informed dietary and lifestyle choices – Individualized presymptomatic medical therapies, e.g., anti-hypertensive agents before hypertension develops, anti-schizophrenia agents before schizophrenia develops, etc. – Prescribing medications based on pharmacogenetics/pharmacogenomics

The Benefits of Genomic Medicine Detect disease at an earlier stage, when it is easier to treat effectively; Enable the selection of optimal therapy and reduce trial-and-error prescribing; Reduce adverse drug reactions; Increase patient compliance with therapy; Improve the selection of targets for drug discovery and reduce the time, cost, and failure rate of clinical trials; Shift the emphasis in medicine from reaction to prevention; Reduce the overall cost of healthcare.

Course Description The course is intended to provide an accelerated review of the basics of genetics and molecular biology followed by a more in-depth coverage of medical genetics topics.

Course Description The first part will cover principals of Mendelian and modern genetics, DNA and gene functions, structure and organization of chromosomes and methods of molecular biology. This part will also review the principals of genome replication, transcription and translation and mechanisms of cell cycle regulation, mitosis and meiosis.

Course Description The second part covers population and quantitative genetics, multi-factorial traits and genetic variations, mutations and inherited genetic disorders and the associated human diseases including autosomal and sex-linked disorders and cancer.

Syllabus 1.Genes, Chromosomes and Heredity 1.Intro to genetics 2.Mendelian and modern genetics 3.Cell cycle, mitosis and meiosis 4.Chromosome organization

Syllabus 2.DNA: Structure, Replication and Regulation of Gene Expression 1.The genetic code, replication and recombination 2.RNA and transcription 3.Proteins and translation 4.Gene mutations and DNA repair 5.Regulation of gene expression

Syllabus 3.Basics of Molecular Biology 1.Recombinant DNA technologies, genetic engineering and proteomics 2.Transgenic animals, gene therapy and cloning 3.The human genome project

Syllabus 4.Genetics of Organisms and Populations 1.Quantitative genetics and multifactorial traits 2.Population genetics

Syllabus 5.Inherited genetic diseases 1.Simple genetic diseases 2.Polygenic diseases 3.Cancer

Syllabus 6.Molecular Therapeutics 1.Genetic screening, linkage and molecular diagnostics: PCR, RFLP & SNPs 2.Genetic counseling 3.Cancer classification and personalized medicine 4.Drug development and pharmacogenetics

Student evaluations Block Exam 1, 30%: Will cover topics 1-3 (60 questions: 25 genetics and 35 Biochem) Block Exam 2, 30%: Will cover topics 4-6 (60 questions: 25 genetics and 35 Biochem NMBE Exam, 30%: Covers all topics Class assignments quizzes and seminars, 10%

Textbook and other recommended readings: 1.Textbook: Human Genetics and Genomics, 4 th edition, Bruce R. Korf & Mira B. Irons, publisher: Wiley-Blackwell. 2.Concepts of Genetics, 10 th edition, William S. Klug, Michael R. Cummings and Charlotte Spencer, publisher: Benjamin Cummings. 3.Genetics in Medicine 6 th edition, Robert L. Nussbaum 4.Medical Genetics for the Modern Clinician, Judith A. Westman 5.Biochemistry, Molecular Biology & Genetics, Michael A. Lieberman (BRS)

Books available at our library Introduction to molecular medicine, 3 rd edition Dennis W. Ross Covers some basics of genetics and molecular biology and discusses select inherited genetic diseases, cancer and molecular therapeutics (Blocks 1-6) Human Genetics, A problem-Based Approach, 2 nd edition Bruce R. Korf Covers select human genetic disorders and some aspects of medical genetics (Blocks 5-6)

Books available at our library Medical Genetics for the Modern Clinician Judith A. Westman Covers briefly the basics of genetics and molecular biology and provides an extensive coverage of medical genetics (Blocks 1-6) Biochemistry, Molecular Biology & Genetics Michael A. Lieberman Provides guidance for preparing to USMLE Step 1 exam

Books available at our library Genetics in Medicine 6 th edition Robert L. Nussbaum Provides extensive cover of the basics of genetics and molecular biology as well as medical genetics (Blocks 1-6

Online Books Concepts of Genetics, 8 th edition William S. Klug Covers the basics of genetics and molecular biology (Blocks 1-4) Genetics, from Genes to Genomes, 4 th edition Leland H. Hartwell Covers the basics of genetics and molecular biology (Blocks 1-4)

Online Books Human Genetics and Genomics, 4 th edition Bruce R. Korf Covers the basics of genetics, molecular biology and medical genetics (Blocks 1-6)

Guidelines for Seminar Series Class will be devided to two groups: A & B Group A: studentsxxx-yyy Group B: studentszzz-vvv The groups will be devided to 5 Study Groups: 1- 5 First meeting, assignment of subjects Second meeting, student presentations

Guidelines for Seminar Series Presentations: Presentations: Each Study Group will me its presentation by Friday before the class. Each presentation should last 10 minutes: 8 min for presentation and 2 min for questions. Two different students from each group will present each time.

Guidelines for Seminar Series Presentations: Presentations: Divide presentation to sections to include: Introduction/Background (1-2 min) Historical perspective (30-60 sec) Disease diagnosis (1 min) Symptoms (1-2 min) Cause and Prevalence Worldwide (1 min) Treatment and management (1-2 min) Future perspectives (30-60 sec) Literature used