HUMAN MOLECULAR GENETICS
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 addresses the Students of the Advanced degree in Industrial Biotechnology. The first part covers basic concepts of cytogenetics, formal genetics, action of the gene, using some examples mostly referring to pathological conditions and to applicative aspects. The second part deals with molecular characterization, organization and regulation of the human nuclear and mitochondrial genome while the concepts of dominance and recessiveness will be dealt with in detail after students have become acquainted with the molecular aspects.
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 sectors with significant applicative aspects such as: pharmacogenetics ( which studies variability in the patients’ DNA sequence with reference to their pattern of response to drugs ), 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 more precise information deriving from the identification of the sequence and function of human genes (Human Genome Project).
Course contents summary
Cytogenetics : structure and function of human chromosomes – cell cycle and mitosis – metaphase chromosome detection techniques – human chromosomes diseases – dose compensation for sexual chromatin.
Formal human genetics: family trees – transmission and segregation of autosomal and sex-related characters - the law of Hardy-Weinberg and its applications.
Action of the gene: discovery and analysis of enzymatic defects in the various metabolic districts – genetics of hemoglobins – blood groups.
The Human Genome project: cultural and organizational aspects - how the human genome was mapped and sequenced - genome project for model organisms.
Organisation of 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.
Human gene expression : transcriptional regulation of gene expression - post-transcriptional regulation - epigenetic mechanisms and remote control – micro RNAs - organization and particular expression of immunoglobulin and TCR genes.
Instability of the human genome: DNA mutation and repair, simple mutations - genetic mechanisms which result in sequence exchanges between DNA repeats - pathogenic mutations - pathogenic potential of repeated sequences - DNA repair.
Human genetic diseases : loss of function mutations – gain of function mutations - 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.
P. SUDBERY – Genetica Molecolare Umana - Zanichelli
T.STRACHAN, A.P.READ – Genetica Umana Molecolare – UTET
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