Integrated Course of HUMAN AND MEDICAL GENETICS
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1 Integrated Course of HUMAN AND MEDICAL GENETICS Scientific Fields: MEDICAL GENETICS (MED/03) APPLIED BIOLOGY (BIO/13) European Credit Transfer and Accumulation System = 7 Coordinator: Prof. BRUNELLA FRANCO, Department: Medical translational sciences, Ed.11, phone: , brunella.franco@unina.it. Didactic Secretariat: Faculty Position Scientific Fields: Auricchio Alberto Ballabio Andrea Capasso Mario De Vita Gabriella Franco Brunella Fraldi Alessandro Iolascon Achille Napolitano Gennaro ucio Russo Roberta Settembre Carmine Surace Enrico professor Phone MED/ MED/ Researcher MED/ Associate Reception (day/time/building) Mon CEINGE Lab Wed MED/03 Ed 19 A MED/ alberto.auricchio@unina.it andrea.ballabio@unina.it mario.capasso@unina.it gdevita@unina.it brunella.franco@unina.it Researcher MED/03 alessandro.fraldi@unina.it MED/ Friday 15:00 18:00 Ed. 19 achille.iolascon@unina.it Researcher MED/03 gennaro.napolitano2@unina.it BIO/13 Ed 19 Researcher MED/ Wed CEINGE Lab 3 Researcher MED/ Associate MED/ nitsch@unina.it roberta.russo@unina.it carmine.settembre@unina.it enricomaria.surace@unina.it 1
2 EDUCATIONAL OBJECTIVES The course focalizes on the study of genetics applied to cells, individuals, families and general population for the comprehension of human physiopathology. We aim to train medical doctors who can: Recognize transmission of hereditary normal and pathological characteristics, determine the models of transmission and assess the probability of occurrence in the offspring; Understand the importance of genetic diseases for individuals and their families; Be aware that advances in molecular genetics can have an immediate impact on life and well-being of patients and their families; Recognize the impact of new knowledge in medical genetics on professional responsibilities of physicians towards patients; Know how to give patients all available choices to deal in the best possible way with genetic disorders; Appreciate the need for a doctor to continuously integrate the knowledge of basic sciences with clinical practice in the patient s care; Be aware of the ethical issues regarding medical genetics; Be aware of the need for genetic counselling and supportive care for patients undergoing genetic testing. CORE CURRICULUM Mendelian transmission of hereditary characteristics. Alleles and loci. Dominant and recessive disorders. Homozygosity and heterozygosity. The analysis of family trees. Factors affecting the expression of genes (modifier genes, imprinting, etc.). Penetrance and variable expressivity. The mitochondrial transmission. Anticipation and imprinting in genetic diseases. Calculation of the genetic risk for Mendelian traits. Mutations: different typology and effect of mutations. Haploinsufficiency. DNA polymorphism. The molecular mechanisms of genetic recombination. Maps and genetic linkage analysis. Chromosomal aberrations. Contiguous gene syndromes. The multifactorial nature of normal and pathological characters in individuals. Quantitative genetics. Epistasis. The calculation of the empirical risk for multifactorial traits. Polygenic inheritance and multifactorial diseases. Regulation of gene expression. Basis for developmental genetics. Epigenetic inactivation of the X chromosome and the genetic control of the cell cycle. Basics of Cancers genetics. Familial syndromic tumours. Loss of heterozygosity. The importance of mirna in cancer genetics. Hardy-Weinberg equilibrium. Population genetics: selection, drift, founder effect and heterozygote advantage. The impact of Darwinism in medicine. The impact of the human genome project in human and medical genetics. Disease gene identification. Functional genomics. NGS approaches in human and medical genetics. Pharmacogenetics. Therapeutic approaches to genetic diseases. Animal models in human and medical genetics. Genetic counselling, prenatal diagnosis. PRELIMINARY KNOWLEDGE Previous knowledge on Molecular and Cellular Biology, Histology, Human Embryology and Biochemistry is required. PROPAEDEUTIC COURSE Molecular and cellular Biology, Biochemistry EXAMS Oral examination TEXTBOOKS Nussbaum, McInnes, Willard, Thompson & Thompson Genetics in Medicine 8th edition, Elsevier Tom Strachan, Andrew Read. Human Molecular Genetics, Fourth Edition 4th Edition, Garland Sciences Tom Strachan, Goodship, Chinnery. Genetics and Genomics in Medicine, Garland Sciences. Other supporting didactic material available at the web-site of Course Coordinator. 2
3 Week Day ( ) Topics of the lessons Teacher Monday 5.3. Tuesday 6.3. Wednesday 7.3. Thursday 8.3. Friday Introduction to Medical genetics. Mendel laws and implication for medical genetics. Mechanisms of mutations. Mutation nomenclature. Pedigrees. Autosomal dominant and recessive inheritance. Haemoglobinopathies and thalassemia. Haemoglobin Lepore. alfa thalassemia. Prenatal diagnosis in thalassemia. Fraldi A De Vita G Monday X-linked inheritance (dominant and Tuesday Wednesday recessive). The examples of Muscular dystrophy and haemophilia. X inactivation and genetic diseases. Thursday Exceptions to mendelian inheritance (incomplete penetrance and variable Friday expressivity). Diseases due to trinucleotide expansion. Mitochondrial disorders. Genomic imprinting and associated diseases Monday Tuesday Wednesday Thursday Friday Techniques in molecular genetics (Southern blotting, PCR, electrophoresis, restriction enzyme analysis, DNA chip, sequence analysis). Next generation sequencing. Genetic tests. Diagnostic, predictive and carrier testing. Risk assessment Methodology in molecular diagnosis. Approaches to the diagnosis of genetic diseases. Multifactorial disorders Capasso M Napolitano G Monday Tuesday Wednesday Thursday Friday Population Genetics. General principles and tools (Hardy Weinberg) Behavioural genetics. Evolutionary genetics. Darwin and Darwinism: impact in genetics - 3
4 5 2-6 April 6 9/13 April Monday 2.4. Tuesday 3.4. Wednesday 4.4. Thursday 5.4. Friday 6.4. Pedigree interpretation and examples of risk assessment. Monday 9.4. Meiosis (Gametogenesis in males and Tuesday Wednesday females) Chromosomes structure Karyotype Techniques for standard and molecular cytogenetic analyses - CGH array. Thursday Quantitative chromosomal disorders Euploidy and aneuploidy Trisomy disorders Friday in humans April April Monday Qualitative Chromosomal disorders Balanced rearrangements: Inversions, Tuesday Wednesday Thursday Friday reciprocal translocations Unbalanced rearrangements: deletions, unbalanced translocations, isochromosomes, ring chromosomes Cell cycle. Oncogenes and oncosoppressors Monday Tuesday Wednesday Thursday Friday Progress test Cell cycle Oncogenes and oncosoppressors Gene expression control. Epigenetics Transcriptional modulation microrna De Vita G 9 30 April-4 May Monday Tuesday 1.5. Wednesday 2.5. Thursday 3.5. Friday 4.5. Drugs that modulate gene expression - Tumour markers and therapeutic targets The human genome project. Structure and function of the human genome Functional genomics - Available Databases and their use in medical genetics M Capasso 4
5 May Monday 7.5. Tuesday 8.5. Wednesday 9.5. Thursday Friday Pharmacogenomics and pharmacogenetics Adult and paediatric tumours: clinical phenotypes and molecular mechanisms - Hereditary tumours Human and medical genetics in the pre- and post-genome era (disease gene identification. Human malformations M Capasso G De Vita May Monday Tuesday Wednesday Thursday Friday Developmental biology - Signal transduction pathways critical for human development Examples of developmental disorders Bioethical issues, Genetics counselling, Prenatal diagnosis Napolitano G May Monday Tuesday Wednesday Thursday Therapeutic approaches in genetic diseases. Cell therapy and gene therapy Animal models in human and medical genetics Friday
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