CODE 104196 ACADEMIC YEAR 2024/2025 CREDITS 6 cfu anno 1 BIOLOGIA APPLICATA E SPERIMENTALE 11158 (LM-6) - GENOVA SCIENTIFIC DISCIPLINARY SECTOR BIO/18 LANGUAGE Italian TEACHING LOCATION GENOVA SEMESTER 1° Semester MODULES Questo insegnamento è un modulo di: BIOTECHNOLOGY AND MOLECULAR GENETICS TEACHING MATERIALS AULAWEB OVERVIEW The course aims to provide students with advanced knowledge in human genetics, necessary to tackle, with appropriate cultural tools, the study of modern genetics. Teaching takes place mainly through frontal lessons. AIMS AND CONTENT LEARNING OUTCOMES The teaching of human molecular genetics concerns the organization and expression of the human genome, molecular methods for the study of gene function and therapeutic approaches for the treatment of genetic diseases. AIMS AND LEARNING OUTCOMES The teaching of Human Molecular Genetics aims to deepen the knowledge and understanding of the biological and genetic mechanisms that control and regulate gene expression, both during normal cell growth and in the case of neoplastic transformation. Tools will be provided to understand the main strategies and techniques of molecular genetics used for the study of genes and genomes. The student will have acquired theoretical and methodological skills that will allow him to apply the correct study methods to solve specific problems in the field of human molecular genetics. PREREQUISITES Knowledge of the basic concepts of genetics and molecular biology is needed to address the content of teaching. TEACHING METHODS The subject matters of the course will be explored in depth through lectures with extensive discussion of the topics based on scientific articles. Students who have valid certification of physical or learning disabilities on file with the University and who wish to discuss possible accommodations or other circumstances regarding lectures, coursework and exams, should speak both with the instructor and with Professor Sara Ferrando (sara.ferrando@unige.it), the Department’s disability liaison. SYLLABUS/CONTENT The module program includes the presentation and discussion of the following topics: - DNA ANALYSIS METHODS: DNA amplification methods; current principles and applications of nucleic acid sequencing; NGS; aCGH; analysis of epigenetically modified regions. - STUDY OF GENE FUNCTION: Analysis of gene expression by NGS on whole tissue or single-cell, gene inactivation, identification of molecular partners. - HUMAN GENOME: Composition: genes coding for polypeptides, RNA genes, tandemly repeated sequences and interspersed repeated sequences; mitochondrial genome; microsatellite instability mechanism; role of gene and intragenic duplication in genome evolution. - ORGANIZATION OF DNA: Histones, nucleosomes, euchromatin and heterochromatin (constitutive and facultative); chromatin and eukaryotic chromosomes; identification of chromosomal territories. - CENTROMERES: Structure and function of centromeres and kinetochores; mitotic checkpoint. - TELOMERS: DNA replication at the end of chromosomes and telomere erosion; structure and function of telomeres; telomeric minisatellite; telomerase and shelterin; structure of the “t-loop”; fusion and instability of chromosomes due to telomerase deficiency (NHEJ). - CHROMATIN MODIFICATION AND EPIGENETIC FACTORS IN GENE REGULATION: Epigenetic mechanisms (DNA methylation, histone methylation and acetylation) and role; proteins involved in DNA methylation and histone modification; epigenomes; genomic imprinting; Long non-coding RNAs. - INACTIVATION OF THE X CHROMOSOME: Importance of gene dosage; inactivation of the X chromosome in mammals; X chromosome inactivation center; mechanism of inactivation of the X chromosome; pseudoautosomal regions of the sex chromosomes. - ORIGINS OF DNA SEQUENCE VARIABILITY Endogenous errors in DNA replication, chromosome segregation and recombination errors; exogenous damage. - DNA REPAIR Repair of single and double strand DNA damage; hereditary disorders of DNA repair mechanisms. - GENETICS AND GENOMICS OF CANCER: Characteristics and capabilities of tumor cells; oncogenes and tumor suppressor genes; oncogene activation mechanisms (amplification, point mutations, chimeric gene translocation, translocation into transcriptionally active regions); genes involved in cell cycle control; genomic instability and epigenetic dysregulation in cancer; somatic mutation theory (SMT). - EFFECTS OF GENETIC VARIABILITY ON THE PHENOTYPE Neutral effects and harmful effects; functional variability, positive selection and adaptive evolution. - NGS-BASED DIAGNOSIS: characterization of genetic variants and prioritization of pathogenic variants; cfDNA analysis; NGS for structural variants. RECOMMENDED READING/BIBLIOGRAPHY - T. STRACHAN, J. GOODSHIP. P. CHINNERT, Genetica & genomica, Zanichelli, 2016 - T. STRACHAN, A. P. READ, Genetica molecolare umana, Zanichelli, 2012 Selected articles, links and presentations will be available on AulaWeb at the end of each cycle of lessons dedicated to a topic of the program. TEACHERS AND EXAM BOARD SILVIA VIAGGI Ricevimento: Students can request an appointment for clarification by sending an email to silvia.viaggi@unige.it EMANUELE BOSI Ricevimento: Students can request an appointment for clarification by sending an email to emanuele.bosi@unige.it Exam Board SONIA SCARFI' (President) SILVIA VIAGGI (President) EMANUELE BOSI MARCO GIOVINE MARINA POZZOLINI (Substitute) LUIGI VEZZULLI (Substitute) LESSONS LESSONS START Lessons will take place during the first semester for the human molecular genetics module and in the second semester for the biomedical biotechnology module. For start of lessons and timetable please consult the following link: http://www.distav.unige.it/ccsbio/orario-lezioni. Class schedule HUMAN MOLECULAR GENETICS EXAMS EXAM DESCRIPTION The exam consists of an oral test, during which the student will answer three questions posed by the teachers on: 1) topic chosen by the student with in-depth analysis of one of the topics addressed in class through the presentation of a scientific article or a reviews; 2) theoretical topic present in the program; 3) interpretation of the results of a genetic analysis present among the contents of the module. ASSESSMENT METHODS During the oral interview, the learning of the knowledge passed on to the student and the verification of the competences that the course aims to transfer to the students, each teacher for their own module. FURTHER INFORMATION Constant attendance is recommended.