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M2 Medical Genetics
2012-2013
Co-Course Directors:
G. Bradley Schaefer, M.D, FAAP, FACMG.
Professor of Genetics and Pediatrics Founding Director, Division of Genetics Committee for the Future Endowed Chair in Genetics, Arkansas Children's Hospital Director, Section of Genetics and Metabolism Department of Pediatrics Mail Slot: 512-22 Office: ACH Administration building, 4009 (4th floor) E-mail: schaefergb@uams.edu Work phone: 501.364.2971

Maha (Mahendran) Mahadevan, D.V.M., Ph. D., M.B.A., Associate Professor


Department of Obstetrics and Gynecology and Medical genetics Co-Course Director, Medical Genetics, Co-Chair, UAMS Institutional Review Board, Laboratory Director, UAMS ART Tissue Bank, Mail Slot: 518 Office: Barton building 5R08 (5th floor) E-mail: Mahadevanmahendran@uams.edu Work phone: 501.686.6359 (If no response, phone: 501.837.0689 or 225.9083)

Course Coordinator:
Michelle Haygood,
Executive Assistant Division of Medical genetics M2 Genetics Course Coordinator Mail Slot: 514 Office: Freeway Medical Tower, 6th floor E-mail: Haygoodmichelle@uams.edu Work phone: 501 526 4020

Table of Contents
Table of contents ..................................................................................................................................... 2 Genetics Faculty ....................................................................................................................................... 3 Course Overview ..................................................................................................................................... 4 Course Goals ..................................................................................................................................... 4 Competencies ................................................................................................................................... 4 Mission statement ............................................................................................................................. 4 Hot genetic diseases.5 Introduction ....................................................................................................................................... 7 Medical genetics terms (glossary) ....9 2011 Topic schedule .......................................................................................................................... 13 Learning Objectives ................................................................................................................................. 15 Medical Knowledge ........................................................................................................................... 15 Patient care ....................................................................................................................................... 16 Interpersonal and Communication Skills .......................................................................................... 16 Professionalism ................................................................................................................................. 16 Objectives of lectures and online modules ..................................................................................... 16 Course Format ......................................................................................................................................... 21 Lectures ............................................................................................................................................. 21 Team based Learning (TBLs) .. 22 Online modules ................................................................................................................................. 22 Tutorials and review 22 Required/Recommended Materials ....................................................................................................... 21 Textbooks ......................................................................................................................................... 21 Helpful Websites ............................................................................................................................... 23 Examinations and Other Graded Activities ........................................................................................... 24 Examinations ..................................................................................................................................... 24 Professionalism ................................................................................................................................. 25 Written Examinations ....................................................................................................................... 25 Quizzes .............................................................................................................................................. 25 Grading ............................................................................................................................................... 25 Statement of Academic Jeopardy ..................................................................................................... 26 Clinical Application and Professional Experiences (CAPE) ...................................................................... 26 Course Policies ......................................................................................................................................... 26 College of Medicine Policies .................................................................................................................... 27

Genetics Faculty
COM Genetics Faculty
Sue Griffin, PhD

Office
Inst. Aging 3104 M1/312 Freeway 500 512-6

Telephone & eMail


526-5801 griffinsuet@uams.edu 526-7511 harvilleterryo@uams.edu 661-7970 dmhester@uams.edu 364-1430 kempstephenf@uams.edu 364-2966 kahlerstepheng@uams,edu 686-5847 lowerycurtisl@uams.edu 686-6359 mahadevanmahendran@uams. edu 319-2095 mckelveykentd@uams.edu 257-6051 wmetzer@uams.edu 320-1294 nicholsbl@archildrens.org 686-8708 paniaguacarmen@uams.edu 603-1158 etprice@uams.edu 526-2245 ryankevinw@uams.edu 364-1494 saccentesuzannec@uams.edu 526-8000 364-2971 schaefergb@uams.edu 257-6445 schichmanstevena@uams.edu 296-1700 zellmerkatel@uams.edu

Terry Harville, MD, PhD Micah Hester, PhD Stephen Kemp, MD Stephen Kahler, MD Curtis Lowery, MD Maha (Mahendran) Mahadevan, DVM, PhD Co-Course Director Kent McKelvey, MD Walter Metzer, MD Brandi Nichols, MS Carmen Paniagua, PhD Elvin Price, PharmD, PhD Kevin Ryan, MA, JD Suzanne Saccente, MD Jeffrey Sawyer, PhD Brad Schaefer, M.D. Co-Course Director Steven Schichman, MD, PhD Kate Zellmer, MS

512-22 Shorey 5/22C Barton 5R-08

Freeway 622 Neurology, Spine Center ACH Ed II5/138 C Biomed II B2380 ACH/CPH ACH H5105-1 Freeway 218
ACH Admin G3064

VA LR 2E-129 Freeway 7/500

Course Overview
Course Goals
Medical genetics is a 24-month long course that begins in the M1 Fall term and extends into the M2 Spring term. The primary goal of the course is to provide the students with a basic understanding of Medical genetics and learn how to apply the concepts and principles in clinical situations. This knowledge serves as a foundation for the remainder of the student's medical education and future practice of medicine.

Competencies
UAMS College of Medicine Competencies Gross Anatomy Competency Trait Competency Covered in Methods of Assessment the Course Medical Knowledge Lecture; Team based MCQ quizzes and exams Learning (TBLs), Online module Patient Care Patient session, TBLs, Required attendance and participation and discussions Professionalism Emphasized Faculty and peer observation Interpersonal and Emphasized Faculty and peer observation Communication Skills Medical Informatics No n/a Population Health and Lecture; TBLs, Online MCQ quizzes and exams Preventive Medicine module Practice-Based and No n/a Systems-Based Medical Care NOTE:

Mission Statement: Over the course of the freshman and sophomore year, the student will gain an understanding of the basic concepts of medical genetics as a foundation for the practice of clinical medicine. We have focused the course based on guidelines from the Association of Professors of Human Genetics and Medical Genetics and The American Society of Human Genetics http://www.aphmg.org/pdf/Med%20Competencies.pdf , and high yield USMLE Step1 topics. (See Medical Genetics USMLE Step 1 Review posted on Oasis, O2 or BlackBoard, BB). Also, we will have two hour Step 1 review and provide self practice test on BB or Exam Soft (one with feedback explanation at the end of spring semester).

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Topics covered include: patterns of inheritance, population genetics, cytogenetics, molecular genetics, developmental genetics, genetic counseling and clinical genetics (pediatric dysmorphology, metabolic genetics, cancer genetics and the genetics of common disease). Specific diseases will be discussed as examples of the above concepts but the gamut of testing options and spectrum of diagnosis seen in clinical genetics is beyond the scope of this course. Unique ethical, legal and social implications brought about by genetic testing will also be discussed in specific lectures and woven throughout this course in collaboration with your ethics course. Please see the list of HOT genetic diseases/disorders below (also posted in O2). We generated the list from the Step 1 review books, text books and our experience. We will cover as many important diseases/disorders as possible. However, it will not be possible to cover all the diseases within the contact time allotted. Therefore, please make sure that you keep a tally and learn the genetic aspects of all these conditions from other courses (Biochemistry, ICM, pathology etc.), the text book and other sources. If you anyone have difficulty finding at least some information before your Step 1 Exam, and definitely before you graduate.

Hot genetic diseases, disorders and syndromes:


Need to know in detail all diseases that are highlighted. For all others, should be able to describe the genetic mechanisms involved in the disease.

Common disorders (single gene or multifactorial):


1. Adult polycystic kidney diseases 2. Cystic fibrosis 3. Duchene muscular dystrophy 4. Becker muscular dystrophy 5. Familial hypercholesterolemia 6. Fragile X 7. Gaucher 8. Hemophilia 9. Marfan Syndrome 10. Neurofibromatosis type 1 11. PKU 12. Hemochromatosis (most common genetic disease)

Polygenic and Multifactorial (Complex) disorders:


13. Alzheimer 14. Diabetes 15. Asthma 16. Arthrosclerosis, heart disease and stroke 17. Hypertension 18. Colon cancer (FAP and HNPCC) 19. Breast cancer

6 20. Acute lymphocytic leukemia 21. Pancreatic cancer 22. Prostate cancer 23. Autism 24. Cleft clip with or without cleft palate 25. Club foot 26. Congenital heart disease 27. Neural tube defects 28. Pyloric stenosis 29. Deaf 30. Congenital adrenal hyperplasia 31. Alcoholism 32. Fetal alcohol syndrome 33. Bipolar affective disorder 34. Schizophrenia 35. Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)

Chromosomal:
36. Trisomy 21 (Down syndrome) 37. Trisomy 13 38. Trisomy 18 39. Klinefelter XXY 40. Turner syndrome 45,X 41. Del22q 42. Chronic myeloid leukemia (CML) 43. Ewing sarcoma 44. DiGeorge syndrome 45. VeloCardio facial syndrome 46. Cri-du-cat syndrome

Single gene disorders and other atypical:


47. Prader-Willi syndrome 48. Angelman syndrome 49. Long QT syndrome 50. Hearing loss (Connexin 26) 51. SCID 52. Pompe 53. MCAD 54. Alkapturia 55. Maple syrup 56. Achodroplasia 57. Osteogenesis imperfect a type I

7 58. Fabry 59. Hemophilia A & B 60. Thalassemia 61. Huntington 62. Muscular dystrophy 63. Hereditary spherocytosis 64. Multiple endocrine neoplasias (MEN) 65. Neurofibromatosis type 2 66. Tuberous sclerosis 67. Von Hippel-Lindau disease 68. Bruton-type agammaglobulinemia 69. Wiskot-Aldrich syndrome 70. G6PD deficiency 71. Occular albinism 72. Lesch-Nyhan syndrome 73. Hunter syndrome 74. Williams 75. Hurler 76. Tay-sachs 77. Galactosemia 78. Friedrich ataxia 79. Myotonic dystrophy 80. Retinoblastoma 81. Alpha 1-Antitrypsin deficiency 82. Albinism 83. Hypophosphatemic rickets

Mitochondrial
84. MELAS, 85. LHON, Lebers hereditary optic neuropathy 86. Kearns-Sayre syndrome 87. MERRF, Myoclonic epilepsy and ragged red fiber disease
Introduction:

The Medical Genetics course is designed to take the students basic knowledge of genetics (obtained as an undergraduate) and demonstrate its application in clinical medicine. Several basic concepts will be emphasized: - the need for understanding clinical genetic principles regardless of anticipated specialty - the phenomenal rate of change in genetic information - applying information about the genetic basis of disorders towards diagnosis, treatment and prevention.

8 An active knowledge of around 1500 - 2000 words is sufficient to be considered fluent in a language. In your first 2 years of medical school you will increase your vocabulary by 3 times this much. You will literally learn the foreign language of medicine. Thus one of the expectations for this part of the core is to learn the language of medical genetics. Some of this will be review, other parts will be new. A major expectation of this course is that you have a strong functional knowledge of all of the definitions provided to you in the Glossary of Clinical Genetics Terms (see in O2 or BB). By functional knowledge, we mean more than just regurgitating definitions back. Our tests questions will require you to understand the terms and then apply them. Yes, you will be asked to think, not just memorize. We are always asked how much of the material in the text do I have to know? or why do we need to buy another book?. We will require a textbook this year (Thompson and Thompson; see under Course information). We have three goals for this course: 1) make sure that you know what you need to know about medical genetics to pass this course, 2) pass USMLE Step 1 boards, and 3) be a competent and well trained physician. We cant give you all of the information that we need to cover in the number of lectures we have. What we would require then is that you consider using the Thompson and Thompson textbook and reference books in the following ways: 1) To read and fully comprehend the required chapter pages from the textbook including the cases (Thompson and Thompson), listed under the learning objectives. 2) To review any of the concepts and basic principles of genetics that you are not completely clear about. 3) To clarify any unanswered questions raised in the lectures, Online self-directed learning modules (Online modules) posted in O2 or BB, Quizzes, practice tests etc. 4) To gather the pieces of information which arent covered in lectures, Online modules etc. 5) The clinical case studies in the Textbook and the reference books are excellent. They show how multiple genetic principles can apply to a single disorder. We would encourage you to review all of them whether required or not. If you understand those, you can feel comfortable that you have a good grasp of the information. Our lectures, TBLs and Online modules are designed to clarify complex concepts and provide clinical examples of how they apply in the real world of medicine. The clinical examples we use in our lectures are there to illustrate concepts. We will usually not be asking you any test questions about the details of the features of a particular disorder. However, there may be questions on USMLE Step I boards about certain syndromes. These are almost always questions about chromosomal syndromes. Thus, for the test questions we submit for you exam on this course, usually, there will be no such questions. We would however recommend that you review the major human chromosomal disorders for Step I boards.
Board-certified MD geneticists are members of the American Board of Medical Specialties. However, recent advances dictate that all physicians be knowledgeable in current medical genetics and understand underlying principles of human genetics. Genetics is a study of variations and similarities of all organisms. Human genetics is a branch of genetics that focuses on clinical practice across all organ systems, periods of life, disease entities, etc. Medical geneticists provide leadership in the introduction of new technologies, their integration into medical care and monitoring of outcomes. Genetics is

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perhaps the most rapidly evolving area in medicine and the following areas are seeing dramatic growth and specialization: Developmental genetics: the study of genetic control of embryonic development Dysmorphology: the study of patterns of birth defects and their impact on health Cancer Genetics: studying personal and family history, along with physical exam and molecular findings to diagnose, treat and prevent cancer in those patients most susceptible; currently, at the leading edge of preventive medicine. Pharmacogenetics: the role of genetic variation in differential response to pharmaceuticals (includes efficacy and adverse effects). Genetic risk counseling: study of genetics to help physicians care for patients by providing genetic risk information, psychological and educational support. Cytogenetics: study of chromosomes and laboratory testing Molecular/Biochemical genetics: study of structure and function of genes, and laboratory testing, including newborn screening. Population genetics: study of genetic variation in human populations with implications for public health Genomics: study of the genome, its organization and functions

Pre-requisites for M2 Medical genetics: M1 Medical genetics, biochemistry, cell biology and embryology (microanatomy). Please go over these lectures and sessions relevant to medical genetics. 2012 USMLE Examination Content and relevant genetic topics (click on the link below). Some of the genetic topics will be covered by other courses. http://www.usmle.org/pdfs/step-1/2012content_step1.pdf

MEDICAL GENETICS TERMS (Glossary): Need to know these terms and how they are used and or applied.
Alleles: are alternative forms of a gene, or of a DNA sequence, at a given locus. Aneuploid: Having an incorrect number / composition of the chromosomes Anticipation: Tendency of some autosomal diseases to occur at earlier age and or to increase in severity in succeeding generations. Association: two or more malformations, which have been found (on a population basis) to occur together more often than would be predicted by chance, but not necessarily due to a specific causal entity Chromosomal analysis (karyotype), routine: cytogenetic analysis to determine the number and structure of chromosomes as seen through microscopic views of prepared cells from an individual's tissue. (High resolution banding: cytogenetic laboratory method in which the chromosomes are induced to be more elongated, allowing much finer detection of smaller changes in the pattern of banding than usual; also called prometaphase banding) Chromosomal microarray: Sometimes abbreviated as aCGH (array CGH). Also called

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comparative genomic hybridization. Numerous FISH tests imbedded on a microchip and read by a laser. This is a rapid way of looking at submicroscopic duplications or deletions Clinical geneticist: a physician with special training in the clinical evaluation of patients suspected to have genetic conditions and birth defects; clinical geneticists historically came from a variety of backgrounds, such as pediatrics, obstetrics/gynecology, internal medicine, neurology, etc. but newly trained individuals may specialize in genetics alone Codominance: Both alleles are equally dominant as in Blood group, A, B, AB Congenital anomaly: an abnormality present at birth Consanguinity: sharing of a common blood relative by two individuals Cytogenetic: referring to the analysis of chromosomes within cells, by culturing living cells or preparing actively dividing cells from body tissues and use of various identification methods to detect individual chromosome structure Deformation: a congenital structural variation or abnormality which is the result of external physical forces Disruption: a congenital abnormality which is the result of a destructive event or process, leading to incomplete or abnormal formation; Dominant conditions are those expressed in heterozygotes, i.e., individuals with one copy of a mutant allele and one copy of a normal (wild-type) allele. Dominant negative: Mutation that results in a protein that forms a complex with the normal protein produced by normal homologous gene and prevents its function. Dysmorphic: literally, abnormally shaped; refers to a physical feature which is sufficiently different from average as to cause concern Dysmorphologist: a specialist trained in the recognition of physical variations and malformations and their diagnostic and clinical significance ELSI: Ethical Legal and Social Implications (of human genetics). This acronym refers to the complex issues surrounding genetics in clinical medicine. It is also an ongoing specifically funded Federal program to address these needs. Etiology: Specific cause of a disorder Familial: Simply means that a condition runs in the family. Familial disorders may be due to genetic factors, common environment or both. Fluorescence in situ hybridization (FISH): a molecular cytogenetic method in which a molecular probe is linked to a fluorescent dye on the slide; views under a fluorescent microscope reveal presence or absence of the desired region of the chromosome through adhesion of the probe or lack thereof Fragile X analysis: methods for detecting the presence of the fragile site at Xq27.3; historically, this was performed by cytogenetic analysis of cells grown in a special growth medium but this testing has been replaced by molecular methods to detect the number of CGG repeats in the chromosome region, with defined ranges for normal and abnormal results Genetic: A medical condition is said to be genetic if the pathophysiology of the disorder is based in a change in the DNA. Genetic counseling: a process by which individuals or families receive information about genetic disorders or malformations and risks for these conditions after review of family and medical history; includes analysis of diagnostic information, review of natural history of the relevant conditions, options for dealing with risks and enhancement of family decision making through non-judgmental support Genetic counselor: a professional trained in counseling families about genetic conditions, genetic risks and decision-making and adapting to a genetic condition Genetic support group: a group or organization developed around a specific condition or group of

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conditions related to genetics or malformations, in order to provide information and support to families Genetic discrimination: use of information about genetic traits in order to identify at-risk individuals for a different selection process in employment, housing, insurance or other usually non-medical settings; typically used to refer to an unfair selection process by which individuals are denied or presented with barriers to their application, such as much higher premiums for insurance Genetic Heterogeneity: Different mutations causing an identical or similar phenotype Allelic heterogeneity refers to different mutations at the same locus. Locus heterogeneity refers to mutations at different loci. Hereditary: inherited or inheritable through the gametes of biological parents; commonly refers to traits related to a single gene or specific chromosome alteration If both alleles at a locus are identical, the individual is homozygous at that locus (a homozygote for that condition). If the alleles at a locus are different, he or she is heterozygous (a heterozygote). Heteroplasmy: When mitochondria (mtDNA) in a cell is composed of normal and mutated gene resulting in disease above a threshold (variable expression). Imprinting: Phenotype difference due to different gene expression depending on the parent of origin. Linkage disequilibrium: Nonrandom occurrence of alleles at liked loci (2 or more) in populations (as opposed to linkage equilibrium) Loss of heterozygosity: Loss of an allele inherited from a parent (important in cancer). A genetic locus is a specific position or location on a chromosome. Frequently, locus is used to refer to a specific gene. Major malformation or anomaly: a congenital structural abnormality which has significant effect on function or social acceptability; example: cleft lip; in its strictest definition, malformation defines a structural abnormality resulting from an abnormal developmental process, but common usage includes all structural abnormalities as malformations, regardless of cause Medical geneticist: a professional with a doctoral degree and special training in the relationships between genes and disease (see Clinical geneticist) Mendelian inheritance: pattern of inheritance of a genetic trait due to a single gene variation which follows the classical patterns of autosomal recessive, autosomal dominant or X- linked (dominant or recessive) inheritance Microdeletion syndrome: pattern of malformations due to loss of a chromosomal segment containing several consecutive (contiguous) genes; they may be difficult or impossible to detect by routine cytogenetic analysis and usually require high resolution (> 550 band) analysis, a molecular test or a molecular cytogenetic test (FISH) for confirmation; example: 22q11 deletions Minor malformation: congenital structural abnormality which has little functional or societal significance on its own; Molecular (DNA) test: laboratory analysis of an individual's genetic material for a designated piece of DNA coding for a region or gene of interest Monogenic: due to a single gene Monosomy: Having only one copy of a particular chromosome Mosaicism: Two or more genetically different cell lines (tissues) occur in an individual. If the change is not in the parents, it is germ-line or gonadal mosaicism. Natural history: typical course of a medical condition in the absence of specific intervention Pathogenesis : Physiologic process in causing disease Pedigree: a formal diagram of the blood relationships in a family using standardized symbols and nomenclature, indicating specific medical conditions, the status of each family member in relation to pertinent genetic traits (affected, unaffected, carrier, etc.) and additional relevant information necessary to discern possible patterns of inheritance and genetic risk; typically three or more

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generations are recorded Key to Symbols for Pedigree Diagrams: Penetrance: For a given condition, the proportion of patients who show clinical signs of the disorder. Penetrance is disease specific. Some conditrions are completely penetrant. Some show incomplete penetrance. Phenotype: the clinical or behavioral presentation of a genetic variation in an individual Phenotype, abnormal: the clinical presentation of a genetic or malformation disorder in an individual, including associated complications and their severity Phenotype, behavioral: the pattern of behavioral abnormalities and traits associated with a specific genetic or malformation disorder Pleiotropism : Multiple clinical effects of a single gene Polymorphism means the existence of multiple allelic forms at a specific locus Not all loci are polymorphic. In fact, 99.9% of all of our genetic code is identical Polyploid: Having a full extra set (or multiples) of the usual 23 haploid set of chromosomes Proband, Propositus, Proposita The first member in a family to be ascertained. If affected, the individual is the index case. Recessive conditions are clinically manifest only in individuals homozygous for the mutant allele (or compound heterozygotes for two different mutant alleles), i.e., carrying a double dose of an abnormal gene. Recurrence risk: the likelihood that a clinical disorder will occur in additional siblings of the same biological parents Relatives may be: First Degree : Parents, siblings, offspring of the proband Second Degree : Grandparents/grandchildren, uncles/aunts, nieces/nephews. Third Degree : Cousins, etc. Sequence: a pattern of related malformations and/or deformations and/or disruptions such that one initial physical abnormality leads to the occurrence of additional abnormalities in a sequential manner Sex-limited Phenotype The expression of a trait in only one of the sexes, due, for instance, to anatomical differences. Example: Uterine or testicular defects. Sex-influenced Phenotype A phenotype which occurs in both males and females, but with different frequencies. Example: Male pattern baldness. Sex-linked Inheritance Sex-linked genes are those located on either the X or the Y chromosome. Because few genes are known to be located on the human Y chromosome, we will focus on Xlinked disorders. Subtelomeric FISH panel: Panel of 41 individual FISH tests with hybridiziation to the subtelomeric (terminal) regions of the chromosomes Syndrome: a recognizable recurrent pattern of malformations and/or deformations and/or disruptions with one or more specific, defined causes Teratogen: an agent capable of inducing one or more malformations in a developing embryo. Can be environmental exposures or maternal medical conditions. Trisomy: Having a full extra copy (n = 3) of a particular chromosome (e.g. Trisomy 21) Uniparental disomy: when two copies of chromosomes are derived from a single parent and no copies are derived from the other parent. Variable expression: Different degrees of clinical expression given the same genotype

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M2 2012 Topic Schedule (FALL)

Date

Day

Time

Topic

Teaching Format

Instructor

Fundamental 1 8/15 8/15 8/20 8/22 8/29 8/29 9/4 WED WED MON WED WED WED THU 9 AM 10 AM 11 AM 9 AM 9 AM 4 PM 1 PM Atypical inheritance I Atypical inheritance II Disorders of sub-cellular organelles Clinical inborn errors of metabolism Tutorial, review QUIZ 1 (close on SUN 9/2 at midnight) Lecture, textbook Lecture, textbook Lecture, textbook Lecture, textbook Discussion BB or Exam soft Schaefer Schaefer Schaefer Schaefer Schaefer, Mahadevan Mahadevan, Schaefer Mahadevan, Schaefer

EXAM 1
Population and mathematical genetics. Fundamentals of growth Clinical Cancer Genetics 1 & II Cancer Cytogenetics Colorectal cancer Molecular basis of neoplasia Ethical issues in genetics Genetics of common and complex disorders I Genetics of common and complex disorders II Tutorial, Review QUIZ 2 (close on WED 10/3 at midnight) Lecture; Textbook Lecture; Textbook PPT; Textbook, PPT, Textbook, PPT, Textbook, TBL (3 hr) Online module active learning (2 hr) Lecture, textbook Lecture, textbook Discussion BB or Examsoft

Fundamental 2 9/12 9/13 9/17 9/17 9/17 9/25 9/28 10/1 10/1 10/1 10/1 10/5 WED THU MON MON MON TUE FRI MON MON MON MON FRI 11 AM 9 AM 4 PM 4 PM 4 PM 9 AM 9 AM 9 AM 1 PM 2 PM 4 PM 1 PM Schaefer Schaefer McKelvey Mckelvey McKelvey Mckelvey, Bellamy, Schaefer, Mahadevan Hester, Mahadevan, Schaefer Schaefer Schaefer Schaefer, Mahadevan Mahadevan, Schaefer Mahadevan, Schaefer

EXAM 2 Immunology/Hematology: None

FALL BREAK 10/10 to 10/14


Pulmonary: None Renal Vascular: None Cardiovascular: None

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Date Day Time Lecture Topic Teaching Format Instructor

CNS I: None CNS II: None


2/8 2/13 MON THU 1 PM 1 PM Behavioral genetics and free will (this is a required lecture) Lecture, textbook McKelvey Mahadevan, Schaefer

EXAM 8

Musculoskeletal/Skin: None GU
2/19 2/19 2/25 3/1 3/7 TUE TUE MON THU THU 1 PM 2 PM 1 PM 4 PM 1 PM Prenatal screening and genetic counseling Prenatal diagnosis Tutorial, Review QUIZ 3 (close on 3/4 SUN at midnight) Lecture, Textbook, Lecture, Textbook, Discussion BB or Examsoft Zellmer, Lowery Lowery, Zellmer, Schaefer, Mahadevan Mahadevan, Schaefer Mahadevan, Schaefer Online module; textbook Textbook, PPT Textbook, PPT TBL (3 hr) Discussion

EXAM 10
Stem cell biology and therapies and gene therapies Pharmacogenetics Treatment of Genetic Diseases Therapies for Genetics disorders Tutorial, Review

ENDOCRINE (END)
3/11 3/11 3/11 3/18 3/18 3/22 FRI MON MON MON MON FRI 4 PM 4 PM 4 PM 1 PM 1 PM 9 AM Mahadevan Price Schaefer Schaefer, Mahadevan, Price Schaefer, Mahadevan Mahadevan, Schaefer

EXAM 11

SPRING BREAK 3/25 to 3/29


Gastrointestinal (GI) : None
3/22 3/22 4/4 4/4 4/22 5/6 5/6 FRI FRI THU THU MON MON MON 4 PM 4 PM 9 AM 1 PM 1 PM 1 PM 1 PM Pathogenesis of human genetics disorders Genome and genetics based personalized health Pathogenesis and diagnosis of genetic disorders: Tying all together Tutorial and review PPT, textbook PPT, Textbook, TBL (3 hr) Discussion Schaefer Mckelvey Schaefer, Mckelvey, Mahadevan Schaefer and Mahadevan Mahadevan, Schaefer Mahadevan, Schaefer Schaefer, Mahadevan

EXAM 12

Self Practice Test with and without feedback explanation USMLE Step 1 Review 1

BB or Examsoft Lecture/Discussion

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Course Learning Objectives


Medical Knowledge
At the completion of this course the student will be able to: Demonstrate a basic knowledge of medical genetics. Demonstrate basic knowledge of medical genetics terminology. Apply medical genetics knowledge to recognize and solve clinical problems. Recognize when you has reached the limits of your medical genetics knowledge when trying to apply it to understanding clinical problems and be able to utilize resources to obtain needed information in a timely manner. Recognize the medical genetics and laboratory findings related to human health, aging and common diseases. Utilize available resources (faculty, textbooks, internet, etc.) to locate medical genetics information in order to understand how it relates to health and clinical problems.

Patient Care
Attend the required PKU patient session and participate in the discussion Learn the medical genetics clinical situations and cases during and after the lecture, and in the online modules.

Interpersonal and communication skills


At the completion of this course the student will be able to: Work as member of a professional team. Engage in self-evaluation and self-study

Professionalism
At the completion of this course the student will be able to: Demonstrate professional values, attitudes and behavior in all interpersonal interactions with faculty, staff and peers.

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M2 Objectives of Lectures and Online Modules 2012-2013 M2 YEAR Fall 2012 Lectures 1&2: Atypical Inheritance I & II
1) Explain the concept of mosaicism and its clinical implications 2) Describe the variations of typical chromosome behavior including crossing over, lyonization, and contiguous gene deletions. 3) Describe atypical inheritance mechanisms including uniparental disomy, imprinting, genetic anticipation, modifier genes, epigenesis, digenic inheritance, triallelic inheritance and expanding trinucleotide repeats and opposite transcripts. 4) Explain the complex inheritance of a condition such as Beckwith-Wiedeman syndrome Thompson & Thompson: Chapter 7: pg 144-146; Case 4, Beckwith-Wiedeman Syndrome; Case 33, Prader-Willi Syndrome

Lecture 3: Disorders of sub-cellular organelles 1) Describe the major types of sub-cellular organelles understand the primary function of each 2) Describe the major clinical presentations of disorders of each type of organelle 3) Describe the major and unique characteristics of mitochondrial inheritance
Thompson & Thompson: Chapter 7: pg 144-147

Lecture 4: Inborn errors of metabolism (IBEMs) 1) 2) 3) 4) Describe the epidemiology of IBEMs and their clinical impact Describe the major categories of IBEMs Describe the presenting symptoms (by age group) of the IBEMs Recognize the important pathognomonic features of key IBEMs presented

Thompson & Thompson: Chapter 13: 396-401

Lecture 5: Population and mathematical genetics

1. Be able to describe the principles of the Hardy-Weinberg equilibrium. Know the basic assumptions.

17 2. 3. 4. 5. 6. 7. Be able to calculate allele frequencies from a simple binomial problem. Describe what is meant by haplotype Discuss the concepts of linkage, recombination and cross-over Describe what is meant by polymorphism and mutation Describe the basics of genetic mapping techniques Recognize the clinical applications of all the above principles.

Thompson & Thompson: Chapter 9: pg 193-196; chapter 10: pg 207-229.

Lecture 6: Fundamentals of growth 1) 2) Describe the key principles involved in growth Apply and discuss these principles of growth using insights from musculoskeletal genetic disorders and rare syndromes.

TBL 1: Molecular basis of neoplasia A) O2 or BB PPT: Clinical cancer genetics 1 & 2


1) Describe the basic genetic mechanisms which lead to cancer. 2) Discuss clinical examples that exemplify each of the basic mechanisms and the repercussions of their diagnosis. Thompson & Thompson: Chapter 16: pg 461-484

B) O2 or BB PPT 18: Cancer cytogenetics


1) Describe the different types and progression of chromosomal aberrations in cancer 2) Be able to identify the cytogenetic nomenclature designations of classic tumors 3) Discuss the mechanisms by which gene functions can be altered by chromosome aberrations in cancer Thompson & Thompson: See above

C) O2 or BB PPT: Clinical cancer genetics : Colorectal cancer


1) Describe family history patterns of colorectal cancer 2) Describe the causes of colorectal cancer 3) Discuss Genetic testing, diagnosis, prevention and treatment Thompson & Thompson: Chapter 16: 476-477

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O2 or BB Online module: Ethical issues in genetics

1) Identify the ethical issues in genetics 2) Describe the fundamental ethical principles involved in genetics 3) Be able to apply these ethical principles in clinical genetic situations.

Lectures 7 & 8: Genetics of Common and complex disorders

Required reading from Thompson & Thompson: Chapter 8: 151-174; Chapter 12: pg 361364 Cases: 1 (Achondroplacia) & 12 Duchene Muscular Dystrophy; 13 (Alzheimer), 15 (Fragile X Syndrome); 22 (Huntington); 23 (Insulin-dependent Diabetes, Type I); 29 (Neurofibromatosis); 30 (non-insulin dependent diabetes, type II); 37 (sickle cell); 39 (Thalassemia)

Recommend the following PPTs, Wimba recordings on O2 or BB and Text book pages as supplementary learning only O2 or BB PPT : Hemoglobinopathies
1) Describe hemoglobin formation and basic terms 2) Describe the thalassemias including the genetics, clinical presentation and treatment 3) Describe sickle cell disease including the genetics, clinical presentation and treatment Thompson & Thompson: Chapter 11

O2 or BB PPT : Cardiovascular genetics 1) 2) 3) 4) Describe the genetic basis of congenital heart diseases Describe the genetics of vascular occlusion Describe the genetics of cardiomyopathies Describe the genetics of conduction abnormalities

Thompson & Thompson: Chapter 8: 169-174; Chapter 12: pg 361-364

O2 or BB PPT: Genetics of dementia and Alzheimer disease


1) Describe the importance of family history of dementia and Alzheimer 2) Describe causes of Alzheimer

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3) Describe stages of Alzheimer dementia 4) Discuss the genetic testing and diagnosis 5) Discuss prevention and treatment

O2 or BB PPT : Trinucleotide repeat diseases


1) Describe the genetic basis for trinucleotide repeat diseases 2) Describe the mechanism of the two types of trinucleotide repeat diseases, involving exons and introns 3) Describe the concepts of anticipation and parent of origin effect 4) Describe the phenotype of a few common trinucleotide repeat disease Thompson & Thompson: Chapter 7: pg 139-144;

O2 or BB PPT : Musculoskeletal disorders:


1) Recognize common, genetically-transmitted musculoskeletal diseases 2) Describe the genetics of growth and parameters in the assessment of growth Thompson & Thompson: Chapter 12: pg 367-376;;

M2 YEAR Spring 2013

Lecture 9: Behavioral genetics and Free will


1) 2) 3) 4) Describe the basics of behavioral genetics Describe the genetic basis of Psychiatric disorders (schizophrenia, manic-depression) Compare and discuss psychological traits versus disease Describe prevention and treatment implications- broad implications

Thompson & Thompson: Chapter 8: 170-171

Lecture 10: Prenatal screening and genetic counseling


1) 2) 3) 4) 5) Describe the concepts of preconception care, prenatal care, prenatal screening/diagnosis Describe routine prenatal care/genetics clinic: Initial visit and first trimester Discuss screening patients for genetic diseases Discuss genetic counseling principles Describe prenatal screening:

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a. First-trimester screening: Maternal serum screening for Beta hCG and PAPP-A, Nuchal translucency by ultrasound b. Second-trimester screening: Triple screen, Quadruple screen 6) Identify special issues relating to Prenatal genetic testing and counseling. Thompson & Thompson: Chapter 15: pg 443-459

Lecture 11: Prenatal diagnosis


1) Describe prenatal diagnosis including laboratory genetic testing and use of Ultrasound during 1st , 2nd and 3rd trimesters 2) Describe clinical procedures: Amniocentesis, Chorionic Villus sampling, Cordocentesis (PUBS) (can we get any video of the procedures) 3) Discuss pre-implantation genetic diagnosis and Pre-implantation genetic screening 4) Discuss fetal Imaging (Level II ultrasound): 2nd and 3rd trimester. Thompson & Thompson: Same as above

TBL 2: Genetics therapies A) O2 or BB, Online module: Stem cell therapy and Gene therapy
1) 2) 3) 5) 6) Describe the principles of Stem cell therapy Describe the current and future uses of stem cell therapy Describe Principles of gene therapy Describe current and future use of gene therapy Discuss fetal therapy

Thompson & Thompson: Chapter 13: 406-410

B) O2 or BB PPT : Treatment of genetic diseases 1) Describe the current genetic therapies and therapies on the horizon. 2) Discuss the potential pitfalls of the therapies

Thompson & Thompson: Chapter 13: 393-418 except stem cell therapy and gene therapy

C) O2 or BB PPT: Pharmacogenetics 1) Describe the concepts involved in pharmacogenetics.


2) Discuss application of pharmacogenetics with examples

Thompson & Thompson: Chapter 18:497-505

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TBL 3: Pathogenesis and diagnosis of genetic disorders: Tying all together A) O2 or BB PPT: Pathogenesis of genetic conditions 1) Discuss how changes in the DNA produce diseases 2) Describe molecular mechanisms of genetic diseases with examples and tying it all together

Thompson & Thompson: Chapter 12: 345-392; Case 7 (CHARGE syndrome)

B) O2 or BB PPT: Genetics and genomics based personal health 1) Describe individualized medicine: screening and treatment 2) Describe predictive genetic testing 3) Discuss new technologies for diagnosis Thompson & Thompson: Chapter 17:485-495

Course Format
The course will include mainly lectures, TBLs, O2 or BB based modules, assigned and or supplementary reading materials (posted on O2 or BB or internet links). The lecture Power Point slides will be posted on O2 or BB before start of each block or system and revised versions, if any, on the day before the lecture or before. All important and necessary content materials cant be covered in the lectures and online modules. Students are expected to do independent study using all available information including textbooks, websites and journals (literature pubmed search).

Lectures
Lecturers will focus the content on major medical genetics concepts and mechanisms. Clinical correlations will be presented in lecture. The lecture is not intended to present all information; students are expected to study information in the recommended textbooks to supplement material presented in the lectures. When necessary, required or supplementary reading material will be provided. Most lectures will be recorded and archived for review.

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Team based learning (TBLs)


Approximately 40 to 50% of the course content will be delivered by TBLs. TBL including the scoring system used in TBL for the grade will be explained before the start of the Classes. Please make sure to attend that session to learn more about TBL. The required content of the TBL will be pre-assigned and learning objectives provided. Contents could be from textbook, posted articles, online modules and PowerPoint slides (PPT). For some TBLs, students would be able to view the previously recorded and archived lectures. Students would be required to learn the content and comprehend enough to use or apply the knowledge to solve clinical problems or explain clinical situations.

Online modules
Approximately 10% of the course content will be delivered via self-directed online Learning modules. The content in these modules will supplement the lectures and TBLs to better understand the concepts and mechanisms and will be considered testable material in the exams and or in the quizzes.

Tutorials and Review


We will try and schedule one review session before each Exam with genetics questions. Please be prepared to ask any questions at that time.

Required/Recommended Materials
Books
Publisher, ISBN Thompson & Thompson Genetics in Medicine, Saunders, ISBN9781416030805 New clinical genetics, Scion, ISBN: 13-9781904842316 Langmans Medical Embryology, Lippincott Williams and Wilkins, ISBN: 978-0-7817-9069-7 Authors Nussbaum, McInnes, Willard, Edition 7th 2007 7th 2007 11th 2010 Required/Recommended Required

Andrew Read and Dion Donnai Sadler, T. W.

Recommended

Recommended

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Helpful web sites for Genetic Resources General


1. www.ncbi.nlm.nih.gov/sites/omim/ (OMIM; Online Mendelian Inheritance of Man) 2. www.ncbi.nlm.nih.gov/sites/GeneTests ; www.geneclinics.org ; www.genetests.org (directory for disorders, clinics, laboratories, gene tests, gene banking) 3. www.clinicaltrials.gov/ct2/search (Search all clinical trials) 4. www.genome.gov/policyethics/ (National human genome research institute policy and ethics) 5. www.ncsl.org/programs/health/genetics/chart.htm (Genetics laws and legislative activity) Genetic Tests 1. http://biochemgen.ucsd.edu/ (biochemical genetic tests) 2. http://genes-r-us.uthscsa.edu (Newborn screening)

3. Consent and confidentiality in clinical genetic practice: guidance on genetic testing and sharing genetic information, 2nd edn. Report of the Joint Committee on Medical Genetics: RCP, RCPath, 2011 Family History Tools
1. www.hhs.gov/familyhistory/ (US surgeon generals initiative) 2. www.ama-assn.org/ama/pub/category/2380.html (AMA brochure and questionnaire for prenatal, pediatric and adult patients) 3. www.geneticalliance.org/ws_display.asp?filter=fhh (Genetic alliance tools for consumers)

Resources for patients and Support groups


1. http://ghr.nlm.nih.gov (Good patient resource) 2. http://marchofdimes.com/gyponline/index.bm2 (March of Dimes) 3. www.rarediseases.org (National organization of rare diseases - NORD) 4. http://rarediseases.info.nih.gov/ (Genetic and Rare diseases) 5. www.orpha.net (Rare and Genetic disorders) 6. www.cancer.gov/search/genetics_services (Cancer genetics services directory) 7. www.acmg.net (find a geneticist) 8. www.geneticalliance.org (genetic alliance) 9. www.nsgc.org (National Society of Genetic Counselors)

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Professional Organizations 1. www.acmg.net (American College of Medical Genetics) 2. www.abmg.org (American Board of Medical Genetics) 3. www.ashg.org (American Society of Human Genetics) 4. www.nsgc.org (National Society of Genetic Counselors) Genetics Education and Learning 1. http://learn.genetics.utah.edu/ (Genetic Science Learning Center) 2. www.kumc.edu/gec (Genetics Education Center) 3. www.kumc.edu/gec/geneinfo.html (For genetic professionals) 4. www.nchpeg.org (National coalition for Health Professional Education in Genetics) 5. http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/diseaseindex.sht ml (Dept. of Energy Biological and Environmental Research Program) 6. www.geneticseducation.nhs.uk (National genetics education and development center)

Examinations and Grading


Examinations
Examination M1 Exams 1, 2, 3, &11 Topic Block Points Possible*

M1 Cells and molecules I, II, III; 45% Endocrine and Reproductive. M2 Fundamentals 1, 2, 3; Central Nervous System 1 ; Genitourinary; Endocrine; Gastrointestinal Same as above and Step 1 topics, Self-study Same as above

M2 Exam 1, 2, 8, 10, 11, 12 &13

Customized National Board of Medical Examiners (NBME) M1 TBL 1 & 2 and M2 TBL 3, 4 & 5

20%

M1 Quiz 1-5 and M2 Quiz

Same as above

IRAT = 5% GRAT = 5% PEER evaluation = 5% TBL Total = 15% 15 %

25 1-6 Professionalism Medical genetics course 5% *The faculty reserve the right to remove questions from an examination if they are determined to be flawed. Faculty has the right to change the weightage of grading provided it applied to everyone equitably.

Professionalism:
Since we believe that medical students should be treated as professionals, each of you begins the course with 5 points equal to 5% - for professionalism (these count towards your cumulative quiz/exam grade). Behavior which is unprofessional may include: absence at required lectures or review sessions, delay in completing assignments and quizzes, unprofessional attire when patients are present, and generally being unaware of or disregarding, professional decorum, behavior and attitude. The above behavior may result in a reduction of professionalism points at the discretion of the course directors(s). If any student should lose all 5 professionalism points during the year, a negative non-cognitive professionalism evaluation will also be submitted to the deans office.

Written Exams
On M 2 exam day the entire class will sit for computerized lecture exams (Medical genetics, microbiology, pathology, behavioral science, ICM and or pharmacology) in the morning or afternoon. The written examination questions will be multiple-choice questions (select the best answer). Many written questions will emphasize the clinical application of medical genetics and will often be based on clinical scenarios. Information from all course activities is considered testable material for the written exams.

Quizzes
The quiz questions will be multiple-choice questions (select the best answer). Many questions will emphasize the clinical application of medical genetics and will often be based on clinical scenarios. Information from all course activities is considered testable material for the quiz. Quiz dates are listed in the schedule (page 10) and quizzes are usually time limited (few days) and open-book. Quiz will close at least a day before the Exam day in that block and students will be able to see the quiz results.

Grading
Percent scores are calculated by dividing the total number of points earned by the total points possible. All the scores in M1 exams and quizzes will be kept and added to the M2 year and a final grade will be issued at the end of M2 year. Letter grades are assigned according to the values presented in the following table: Grade A B C D F Percentage 90- 100% 80 89.99% 70 79.99% 65 69.99% < 65%

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Academic jeopardy is defined as follows: If your exam scores drop below the level needed to maintain a C or better in the course, you will receive an email (UAMS) telling you that you are in danger of earning a D or an F in the course. Approximately half way through the course, we will inform you according to the COM policy if you are in academic jeopardy. In this situation, we will provide additional tutorial opportunities by appointment to help you improve. To pass the course, a student must score at least 65% overall in the course. Individual grades are reported for the permanent academic record as either A, B, C, D, or F. Numerical scores are used only to determine the letter grade.

Clinical Application and Professional Experiences (CAPE)


Each lecture, TBL and online module will emphasize the clinical application of the basic science concepts and principles covered. Several clinical cases will be assigned from the Textbook for TBL or lectures. The material presented may be included on the examinations. However, genetics faculty will have or participate in the following special clinical sessions.

DATE Done in M1

TOPIC PKU patient session

PRESENTER Kahler, Nichols

Course Policies
Professional behavior is expected of you in the lecture rooms and during any sessions. Unprofessional or disrespectful behavior will not be tolerated.

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College of Medicine Policies


Policy statements are contained in the College of Medicine Student Handbook for the following topics at http://www.uams.edu/com/students/STDMAN%20generic%20for%20web.pdf

Medical Knowledge
Patient Care Professionalism Interpersonal and Communication Skills Lifelong Learning (Medical Informatics) Population Health and Preventive Medicine Practice-Based and Systems-Based Medical Care

Honor System
Constitution of the Honor System Honor Pledge

Code of Professional Conduct for Medical Students


Medical Student Oath

Academic Policies
Guidelines for Examinations Policy for Missed Examinations for freshmen and sophomores Absence from Classes Policy on Recorded M1 and M2 Lectures or Labs Warning Students of Marginal Performance

Administrative Policies
Inclement Weather Policy Americans with Disabilities Act

Attendance Policy