Learning objectives
Aims of the course is to know:
- the hereditary transmission patterns of monogenic diseases
- the identification of disease genes
- the molecular bases and potential applications of the gene therapy
- the relationship between the patient's genetic component and the response to drugs
- the main applications of DNA analysis in the forensic field
- the main experimental models used in biomedical research
- the genetic tools available for functional analysis of genes in the different model organisms
To understand how the integration of the different experimental models in vivo and in vitro gives specific answers to the different biological problems. To acquire the ability to develop and apply experimental strategies for the resolution of genetics and cell biotechnology problems.
Prerequisites
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Course unit content
HUMAN MOLECULAR GENETICS:
- The human genome, The human karyotype
Genomic and chromosomal mutations and diseases
Other sources of variability: genetic variants.
Molecular pathology and identification of disease-associated genes
Hereditary patterns of monogenic diseases
Genes and cancer: oncogenes and oncosuppressor genes
Genetic polymorphisms in forensic genetics and pharmacogenetics
Gene and cellular therapy
LABORATORY ACTIVITIES
Genetic variants analysis
MOLECULAR GENETICS OF MODEL SYSTEMS IN VIVO AND IN VITRO FOR BIOMEDICAL AND BIOTECHNOLOGICAL RESEARCH:
The genome editing in model organisms
Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Zebrafish, Mouse
Drug discovery
Cell cultures, iPSCs (Induced pluripotent stem cells)
Full programme
HUMAN MOLECULAR GENETICS
Human genome: structure and sequence of the human genome, funamnetals on cells and human chromosomes, human karyotype.
Genomic and chromosomal mutations and diseases: alterations in chromosomes number, structural alterations and their consequences.
Other sources of variability: genetic variants.
Molecular pathology: types of mutant alleles, dominance and recessivity from a molecular point of view.
Identification of disease-associated genes: techniques for disease identification. Multifactorial traits genetics.
Hereditary patterns of monogenic diseases: autosomal recessive, autosomal dominant, X-linked recessive, X-linked dominant, Y-linked and mitochondrial inheritance, complications in Mendelian inheritance.
The two main classes of cancer genes: oncogenes and tumor suppressor genes. Function, type of mutation, activation mechanism.
Genetic variants in forensic genetics and pharmacogenetics. Forensic Genetics: Genetic markers used in forensic science. Methods for the detection of genetic variability. Validity and practicability of the methods used. Determination of sex, origin of the species, individual profile. Paternity, maternity, familiarity test. Interpretation of the results: statistical considerations.
Pharmacogenetics: Genes involved in pharmacokinetics and pharmacodynamics. Polymorphisms in genes that influence the availability of drugs. Genetic polymorphisms. Clinical applications, limitations and future perspectives.
Gene and cell therapy: the different strategies. Nucleic acids with therapeutic function. Methods for gene transfer: viral and non viral systems. Importance of disease models. Examples of clinical trials of ex vivo and in vivo gene therapy. Cells stem and cell therapy.
LABORATORY ACTIVITIES
Genomic DNA extrcation, genotypic distributions and allelic variants analyses through PCR, restriction enzymes digestions and electrophoresis on agarose gel.
MOLECULAR GENETICS OF IN VIVO AND IN VITRO MODEL SYSTEMS FOR BIOMEDICAL AND BIOTECHNOLOGICAL RESEARCH
Genome editing on model organisms: CRISPRCas9.
Saccharomyces cerevisiae: Forward e reverse genetics. Yeast as model organism for the study of mitochondrial genetics and for the study of mitochondrial diseases.
Caenorhabditis elegans: Forward e reverse genetics in C. elegans. Functional analysis by RNAi C. elegans as model organism for the study of human pathologies.
Drosophila melanogaster: Classical genetic techniques. Transformation and cloning mediated by the P element. Methods for the construction of mutants by reverse genetics: insertional mutagenesis mediated by P elements, excision mutagenesis; functional analysis by RNAi. Role of Drosophila in drug discovery and as a model in the study of human pathologies.
Zebrafish: Forward e reverse genetics in Zebrafish. Morpholino tecnique. Knok out of genes by Zn finger nucleases, TALENs and CRISPRs-Cas9. Zebrafish as model organism for the study of human pathologies.
Mouse: Transgenesis.Transgenesis in staminal cells. Knok-out and knok in of genes.
Drug discovery in model organisms.
Cell cultures: primary, stabilized and immortalized cell lines, iPSCs (Induced pluripotent stem cells).
Bibliography
-Philip Meneely- Analisi Genetica Avanzata
ED. McGraw-Hill
-T. Strachan, A.P.Read-
Genetica molecolare umana
Zanichelli
-M.Giacca-Terapia genica
Springer Biomed 2014
-Ricci, Previderè, Fattorini, Corradi-La prova del DNA per la ricerca della verità, Giuffrè Ed
Original papers suggested by the teacher.
Teaching methods
The course includes lectures with powerpoint presentations and laboratory activities. During some lectures scientific articles concerning the problems addressed will be analyzed and discussed in the class. The teaching material used in the lessons will be provided to the student through the Elly platform. Course enrollment is required to access these online resources
Assessment methods and criteria
The acquired knowledge will be verified with a written exam (two hours) in which the student will have to answer three open-ended questions relating to the topics covered in the course.
The knowledge and understanding of the different topics covered during the lessons and the ability to communicate clearly and with language properties, ideas and concepts will be assessed.
Other information
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2030 agenda goals for sustainable development
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