03553 - Medical Genetics

Learning outcomes

The student will acquire the knowledge and methodological tools for the study of human genetic diseases; knowledge of hereditary mechanisms in humans; problems inherent in the diagnosis of genetic diseases; basic notions of some methods of analysis at the molecular and cellular level; the ability to acquire specific skills regarding the choice and applicability of the same to biomedical problems; to understand the significance of the study of modern genetics and to acquire the fundamental analysis tools in the context of the professional skills that characterize the profession.

Course contents

Introduction to the course: medical genetics and what it deals with - glossary and definitions - structure and function, operational concepts - definition and relationship between genotype and phenotype - wild-type allele and mutant allele - dominant and recessive trait transmission. Classification of mutations. Reconstruction of family trees and risk assessment. Symbology of family trees, product and sum rule. Classroom exercises on risk calculation. Genetic diseases: classical mode of inheritance - autosomal recessive inheritance and examples (cystic fibrosis) - autosomal dominant inheritance and examples (achondroplasia) - X-linked inheritance and examples (Duchenne muscular dystrophy). Exceptions to Mendelian inheritance: concepts of clinical heterogeneity and genetic heterogeneity. Triplet expansion diseases and examples: Huntington's disease - concepts of anticipation, premutation, toxicity; X-fragile - role of X methylation and inactivation. Non-canonical modes of transmission. Examples and concepts of imprinting, uniparental and epigenetic disomy (Angelman and Prader-Willi) - Mitochondrial inheritance: matrilinearity, polyplasmy (heteroplasmy and homoplasmy), threshold effect - Concepts of penetrance and variable expressivity with examples. Chromosomal pathology: structural and numerical aberrations of chromosomes with clinical examples. Trisomies and monosomies of autosomes and sex chromosomes. Balanced and unbalanced translocations: reproductive outcome of carriers of balanced translocations. Robertsonian translocations: reproductive mechanisms and problems. Classical and molecular cytogenetic techniques. FISH and its applications. Comparative genomic hybridization (CGH) techniques, technical aspects and its applications in diagnostics. Multifactorial diseases, empirical risk calculation. The role of polymorphisms. Studies on cohorts of twins (concordance and discordance). Evolution of sequencing techniques: from Sanger sequencing to Next generation sequencing techniques. Notes on technological evolutions. Use of genetic and non-genetic databases: NCBI, Pubmed, Gene, OMIM, gnomAD. Bioinformatics tools for the prediction of pathogenicity of protein variants: polyphen2. Bioinformatics tools for primer design and validation: primers3. Genomic browsers: Ensembl and UCSC.

Readings/Bibliography

Thompson & Thompson - Genetica in Medicina. Idelson-Gnocchi editore.

Tobias, Connor, Ferguson-Smith - Fondamenti di Genetica Medica. Pearson editore.

Read A. Donnai D. - Genetica Clinica. 2007 Editore: UTET SCIENZE MEDICHE

Use of textbook is not compulsory.

Teaching methods

Lectures aided by ppt presentations.

Assessment methods

Written test. The structure of the test will vary based on whether it is performed remotely or in person.

The written exam (in person, 1h) consists of three exercises on the calculation of risk that are worth a maximum of 5 points each, and of 12 multiple choice questions on the theoretical aspects that are worth 1.5 points each, with a penalty of 0.5 for no answer and 1 for wrong answer.

The use of the calculator is neither necessary nor permitted.

The written exam (remote, 30 minutes) consists of 22 or 23 multiple choice questions with no penalty for wrong answer, which include short risk calculation exercises. The choice of exam method, in person vs. remotely, it will take place based on the pandemic conditions and the University provisions, and students will be promptly notified.

Teaching tools

Students will be provided with the presentations projected during the lessons in electronic format, after each lesson.

Office hours

See the website of Giuseppe Gasparre