CODE 95306 ACADEMIC YEAR 2023/2024 CREDITS 5 cfu anno 1 MEDICAL-PHARMACEUTICAL BIOTECHNOLOGY 10598 (LM-9) - GENOVA SCIENTIFIC DISCIPLINARY SECTOR MED/03 LANGUAGE English TEACHING LOCATION GENOVA SEMESTER 2° Semester MODULES Questo insegnamento è un modulo di: HUMAN GENETICS AND MOLECULAR PATHOLOGY AND LABORATORY TEACHING MATERIALS AULAWEB AIMS AND CONTENT LEARNING OUTCOMES Knowledge of the mode of inheritance of genetic disorders in humans and the underlying molecular mechanisms. Comprehension of experimental approaches for the detection of genetic factors associated to human diseases. Basic concepts on population genetics. AIMS AND LEARNING OUTCOMES The course aims at deepening into the many pattern of inheritance of genetic disorders and the underlying molecular causes. In addition, we will present the variety of experimental approaches to the study of human genetic disorders, including cytogenetic techniques and novel sequencing technologies. We will also deal with the management of bioinformatic data related to sequencing analysis. We will hence approach basic concepts of population genetics and factors influencing the distribution of variants. Finally, the course will provide information about inheritance of common polygenic and multifactorial disorders and presents methods to identify susceptibility factors. TEACHING METHODS The course is organized in frontal lessons held in English. The topics included in the syllabus will be explained by the professor through PowerPoint presentation, also using examples from scientific papers. Students will be stimulated to ask questions and formulate answers using interactive modalities. SYLLABUS/CONTENT MENDELIAN INHERITANCE AND GENETIC DISORDERS Inheritance in Men: A brief History Monogenic Disorders with Mendelian inheritance Autosomal dominant disorders Autosomal recessive disorders Other Monogenic Disorders Chromosome X inactivation and X-linked disorders Y-linked disorders Mitochondrial inheritance Beyond Mendel. Complex monogenic disorders Genetic Heterogeneity Allelic Heterogeneity Variable expressivity and Incomplete penetrance Lethal alleles Sex-limited traits Dynamic mutations and disease anticipation De novo mutations, gonadal and somatic mosaicisms Imprinting disorders and parent-of-origin gene expression MUTATIONS IN GENETIC DISORDERS Polymorphic variants Classification of Mutations Chromosomal disorders and Cytogenetics Human Karyotype Numerical and structural chromosomal abnormalities: classifications and mechanisms Abnormalities of Sex chromosomes Copy number variants (CNVs) Point Mutations DNA level: base substitution and base deletion/insertion Protein level: Coding mutations Allelic heterogeneity in Cystic Fibrosis, as example Nonsense mediated mRNA decay Protein level: Non-Coding mutations Mutations affecting splicing Intronic mutations affecting non-coding functional elements Functional level: Loss- or gain-of-function IDENTIFYING MUTATIONS IN GENETIC DISORDERS Conventional Cytogenetics for detection of chromosomal abnormalities Karyotyping and chromosome banding International System for human Cytogenetics Nomenclature (ISCN) Cytogenetics in the clinical practice Molecular Cytogenetics for detection of Copy Number Variants (CNVs) Fluorescence in sit hybridization (FISH) Comparative Genomic Hybridization (CGH) DNA microarrays CGH Arrays SNP Arrays DNA microarrays in the clinical practice Sequencing Sequencing methods Maxam-Gilber Sanger Massive parallel Sequencing (NGS) – Short Reads Single Molecule Sequencing – Long Reads Analysis of Sequencing data Genetic Databases and Genome Browsers Applications of Sequencing methods in human genetics Genetic Testing NGS: Exome Sequencing and interpretation of variants in the clinical setting NGS: Detection of Structural Variations (NIPT) Long Reads Sequencing (Repeats and GC regions, De Novo Assembly) POPULATION GENETICS Hardy-Weinberg Equilibrium Factors influencing H.W. equilibrium Mutation Genetic drift Migration Non-random mating Natural selection Neutral Theory Linkage Disequilibrium POLYGENIC AND MULTIFACTORIAL DISORDERS Complex inheritance Variance and Heritability Concordance in twins, relative risk ratio, empiric risks Discontinuous and Continuous traits Mapping of complex traits Association studies Sequencing studies and Gene Burden test RECOMMENDED READING/BIBLIOGRAPHY Lecture notes and reviews covering the whole course will be available for the students in Aulaweb. In addition, students will be provided with files containing genetic problems with solutions Recommended reference textbook: Strachan & Read: Human Molecular Genetics. Bios Scientific Publisher TEACHERS AND EXAM BOARD FEDERICO ZARA Ricevimento: For appointment please write to: federico.zara@unige.it or telephone 010-56363816 PAOLO SCUDIERI Ricevimento: Please, make an appointment by e-mail paolo.scudieri@unige.it, or telephone 010-56362606. Exam Board CLAUDIA CANTONI (President) FEDERICO ZARA (President) RENATA BOCCIARDI ALDAMARIA PULITI PAOLO SCUDIERI NICOLA TRAVERSO CHIARA VITALE LESSONS LESSONS START II semester, March 2022 Class schedule HUMAN GENETICS AND LABORATORY EXAMS EXAM DESCRIPTION The exam is carried out as oral test in English or in Italian, as preferred by the student. The final vote is expressed out of 30. ASSESSMENT METHODS The oral exam, in English or Italian, will allow to test students on most of the content of the course, by assessing their knowledge on human genetics, as well as the acquired ability to connect different topics and to eventually solve genetic problems. Proficiency in English language, if opted by the student, will not be evaluated, but it must be sufficient to show the student’s knowledge of the subjects, with an adequate level of expertise. Exam schedule Data appello Orario Luogo Degree type Note 24/01/2024 14:30 GENOVA Orale 16/02/2024 14:30 GENOVA Orale 19/06/2024 14:30 GENOVA Orale 02/07/2024 14:30 GENOVA Orale 22/07/2024 14:30 GENOVA Orale 11/09/2024 14:30 GENOVA Orale 25/09/2024 14:30 GENOVA Orale