|SCIENTIFIC DISCIPLINARY SECTOR
|Questo insegnamento è un modulo di:
AIMS AND CONTENT
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.
Frontal lessons delivered through multimedia presentations.
The teaching programme provides for the presentation and discussion of the following topics:
- DNA ANALYSIS METHODS: various methods of DNA amplification; current principles and applications of nucleic acid sequencing.
- GENIC EXPRESSION ANALYSIS: use of microarrays; applications via NGS; analysis of epigenetically modified regions.
STUDY OF GENE FUNCTION
Gene expression analysis using NGS, gene inactivation, identification of molecular partners.
Composition: coding genes for polypeptides, RNA genes, repeated tandem sequences and repeated interspersed sequences. mitochondrial genome. Mechanism of expansion of microsatellites and triplet genes. Role of gene and intragenic duplication in genome evolution (involvement of repeated sequences in tandem and interspersed). And comparative genomics.
DNA ORGANIZATION: histones, nucleosomes, euchromatin and heterochromatin (constitutive and optional). chromatin and eukaryotic chromosomes. Identification of chromosomal territories.
Structure and function of the centromeres and kinetochores. Mitotic checkpoint.
DNA replication defect at the end of chromosomes and telomere erosion. Structure and function of telomeres. telomeric mini-satellite. Telomerase and shelterin. Structure of the "t-loop". Fusion and chromosome instability due to telomerase deficiency (NHEJ).
THE MODIFICATION OF CHROMATINE AND EPIGENHETIC FACTORS IN THE GENE REGULATION Epigenetic mechanisms (DNA methylation, methylation and histone acetylation) and their roles. Proteins involved in DNA methylation and histone modification. Epigenomes. Genomic imprinting. Non-coding RNAs.
INACTIVATION OF THE X CHROMOSOME
Importance of gene assay. Inactivation of X chromosome in placental and marsupial mammals. X-chromosome inactivation centre. X-chromosome inactivation mechanism. Pseudo-autosomal regions of sexual chromosomes.
THE PRINCIPLES OF GENETIC VARIABILITY:
- ORIGINS OF VARIABILITY OF DNA SEQUENCE Endogenous errors in DNA replication, chromosomal segregation and recombination errors; exogenous damage.
- DNA REPAIR: Repair of DNA damage on single and double strands. Hereditary disorders of DNA repair mechanisms. Mechanism of "non-sense RNA mediated decay" (NMD).
GENETICS AND CANCER GENOMICS
Characteristics and capacity of tumor cells. oncogenes and tumor suppressor genes. Mechanisms of oncogenic activation (amplification, point mutations, chimeric translocation gene, translocation in transcriptively active regions). Genes involved in cell cycle control. genomic instability and epigenetic dysregulation in cancer. Multistep tumor development process: somatic mutation theory (SMT). Criticism of SMT and development of alternative theories. GENETIC VARIABILITY EFFECTS ON PHENOTYPE: Neutral effects and harmful effects. Functional variability, positive selection and adaptive evolution. NGS-BASED DIAGNOSIS: characterization of genetic variants and prioritization of pathogenetic variants; cfDNA analysis; NGS for structural variants.
- 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
SONIA SCARFI' (President)
SILVIA VIAGGI (President)
DOMENICO COVIELLO (Substitute)
SERENA PATRONE (Substitute)
MARINA POZZOLINI (Substitute)
LUIGI VEZZULLI (Substitute)
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.
The knowledge and skills acquired by students will be evaluated for both modules with an oral exam to verify the level of student preparation and critical skill acquisition in discussing topics of genetic and biotechnological type and ability analysis of experimental problems and possible solutions in the field of applied biotechnology and biomedical research.
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.
Constant attendance is recommended.