HUMAN MOLECULAR GENETICS - GENOTOXICITY
Learning outcomes of the course unit
The current integration of Human Genetics with molecular biology and
bioinformatics gives indications of a future full of promise for biological research
and, consequently, for potential applications to Medicine and Biotechnology. This
course, aimed at students of an advanced degree in Biology, deals with molecular characterization,
organization and regulation of the human nuclear and mitochondrial genome.
Since the most interesting of the applicative aspects obviously regard human
health, special attention will be given to developing the molecular aspects of
monogenic and complex diseases and basic information on the instability of the
human genome (mutation and repair) and on some currently fast growing sectors
such as: pharmacogenetics (which studies, in individuals or in populations,
variability in the response to drugs due to genetic factors), cancer genetics (linked
to the discovery of the increasingly close relationship between somatic mutations
and neoplasias) and finally to the exciting field of human gene therapy that it is
hoped will gain further impetus from the increasingly prompt information coming
from the identification of the sequence and function of human genes (Human
Another aim of the course is to provide a panoramic view of the various aspect of the
environmental mutagenesis and in particular of the environmental genotoxic risk at
which human are subjected. The course provides a detailed overview
of methodologies for monitoring human populations and the environment itself (e.g.,
air, water, soil).
Course contents summary
The Human Genome project: cultural and practical aspects.
Organization of the human genome: nuclear and mitochondrial genomes.
Expression of the human gene: transcriptional regulation of gene expression -
post-transcriptional regulation - epigenetic mechanisms and remote control. Instability of the human genome: DNA mutation and repair. Pathogenic mutations.
Genetic diseases in man: mutations with loss or gain of function. Molecular pathology: from the gene to the
disease and from the disease to the gene. Pharmacogenetics: genes involved in pharmacokinetics and pharmacodynamics - molecular strategies for optimizing pharmacological
Gene therapy: the different strategies for gene therapy - gene therapy for
hereditary diseases, neoplasias and infectious diseases - ethics of gene therapy in man. Genotoxicity: physical and chemical mutagens - environmental contamination and its consequences - detection methods.
The Human Genome project: cultural and practical aspects - how the human genome was mapped and sequenced - genome project for model organisms.
Organization of the human genome: nuclear and mitochondrial genome - organization, distribution and function of human genes (which code RNA and polypeptides) - non-coding DNA with tandem or interspersed repeats.
Expression of the human gene: transcriptional regulation of gene expression - post-transcriptional regulation - epigenetic mechanisms and remote control.
Instability of the human genome: DNA mutation and repair, simple mutations - genetic mechanisms that produce sequence exchanges between DNA repeats - pathogenic mutations - pathogenic potential of repeated sequences - DNA repair.
Genetic diseases in man: mutations with loss of function - mutations with gain of function - the effects of gene dosage - molecular pathology: from the gene to the disease and from the disease to the gene, chromosome diseases - somatic mutations and neoplasias: oncogenes and tumour suppressor genes, genome stability and cell cycle control.
Pharmacogenetics: genes involved in pharmacokinetics and pharmacodynamics - polymorphisms in the genes that affect drug availability - genetic polymorphisms of receptors and repair systems - molecular strategies for optimizing pharmacological therapy.
Gene therapy: the different strategies for gene therapy - gene therapy for hereditary diseases, neoplasias and infectious diseases - ethics of gene therapy in man.
Genotoxicity: molecular basis of DNA alterations
- chemical and physical mutagens
metabolism of xenobiotics
- Sources of genotoxic pollutants
- natural and manmade mutagens and cancerogens in: environmental samples (air,
soil, water, etc.)
- biomarkers and bioindicators
- methods and testing strategies: in vitro and in vivo mutagenicity tests.
T.STRACHAN, A.READ - Genetica molecolare umana - Zanichelli; Mutagenesi Ambientale - a cura di Lucia Migliore - Zanichelli;J.J.PASTERNAK -
Genetica Umana Molecolare - Zanichelli
E.H.McCONKEY - Genetica Umana. Una prospettiva molecolare - Zanichelli
P.LOLLINI, C.DE GIOVANNI, P .NANNI - Terapia genica - Zanichelli
P.PARHAM - Immunologia - Zanichelli
B.LEWIN - Gene X - Pearson Education International
The course will be conducted through lectures on specific topics, with the help of power point presentations. Some scientific papers about the problems faced will also be analyzed and discussed. The course material will be made available, it is nevertheless strongly recommended the use of specific books for study.
Assessment methods and criteria
The assessment will be done through a final oral exam.
The oral examination will aim to test the knowledge and ability of understanding of the various topics covered during the lessons and to highlight the ability of the student to make connections between topics. With regard to scientific articles analyzed in the classroom, the students must also demonstrate their ability in analyse the scientific subject treated, their understanding of the experiments carried out, the results obtained and their interpretation. This examination will assess the students' ability to apply knowledge to specific problems, to connect the various acquired knowledge and to give a critical judgment and also their ability to communicate the knowledge learned.