03553 - Medical Genetics (L-Z)

Learning outcomes

The course aims to present the recent innovations obtained in the last years in the field of Medical Genetics and to offer the possibility to transfer this knowledge to clinical practice. At the end of the course the student: - is able to reconstruct family trees, to interpret the segregation of hereditary diseases, to calculate the risk of their recurrence; - knows the linkage analysis and reconstructs the haplotypes; - knows the exceptions to Mendelian inheritance, the principles underlying complex genetic diseases, the methods for the molecular diagnosis of a genetic disease; - knows the purposes and methods to perform genetic counseling.

Course contents

Molecular Genetics.

Human Genetic Analysis: Linkage analysis, DNA polymorphisms and genetic disease mapping, lod score calculation, linkage disequilibrium, association studies, TDT.

Genomics and post-genomics.

Identification of disease genes: Functional cloning and positional cloning, the positional candidate gene approach. The Human Genome Project and the analysis of the human genome sequence for searching new disease genes. Next generation sequencing (NGS) and its clinical applications. International databases and related information.

Clinical Genetics.

Databases in Genetic Medicine: The tools for the access to updated information and databases, the OMIM (On-line Mendelian Inheritance in Man) example.

Genetic counseling: Different types of genetic counseling.

Medical Genetics.

Chromosomal disorders: Anomalies in the number or in the structure of chromosomes. Aneuploidy of sex chromosomes. Molecular cytogenetics for the identification of microdeletion/microduplication syndromes.

Monogenic diseases: Anamnesis and family tree; definition, construction and study of family trees. Calculation of the recurrence risk of a genetic disease.

The exceptions to Mendelian inheritance: problems related to the interpretation of a family tree. Variable expressivity and incomplete penetrance (Ex: Holoprosencephaly). Genetic heterogeneity (Ex: deafness). Digenic inheritance and triallelic inheritance. Late-onset diseases and anticipation (Ex: Huntington's disease). Skewed chromosome X inactivation and X-autosomal translocations. Germinal and somatic mosaicism. Mitochondrial inheritance (examples of mitochondrial diseases). Genomic Imprinting.

Genetic Medicine.

Polygenic diseases: Quantitative and semi-quantitative traits. Evaluation of the genetic component in complex genetic diseases. Strategies for the identification of susceptibility genes.

Clinical Genetics.

Molecular Diagnosis: Molecular diagnosis of a genetic disease. Direct diagnosis. Indirect diagnostic tests. Prenatal Diagnosis.

Oncogenetics: Familial tumor syndromes. Genetic susceptibility to tumors.

Genomics and post-genomics.

Pharmacogenomics.

Readings/Bibliography

Updated Power Point presentations will be provided to students.

The following texts are recommended:

E.S. Tobias, M Connor, M Ferguson-Smith "Fundamentals of Medical Genetics, Italian edition by D. Turchetti, P. Magini, M. Seri. Pearson editions.

Neri G, Genuardi M. "Human and medical genetics" Elsevier Masson (third edition)
Strachan T, Read AP " Human Molecular Genetics" II edition UTET.

Teaching methods

The course consists of frontal lessons (2 CFUs). Optional exercises and seminar activities will also be carried out.

Assessment methods

The final examination aims to assess the achievement of educational objectives. It consists of an oral test on the program topics.

Teaching tools

At the beginning of the course a self-assessment test will be carried out and it will be returned to the students at the end of the course. During the course, Power Point presentations will be presented. This educational material will be available to the students in a electronic format. Furthermore, ongoing tests will be provided for the preparation of the final evaluation.

Office hours

See the website of Marco Seri