03553 - Medical Genetics

Academic Year 2017/2018

  • Teaching Mode: Traditional lectures
  • Campus: Bologna
  • Corso: First cycle degree programme (L) in Biomedical Laboratory techniques (cod. 8484)

Learning outcomes

At the end of the course, the student possesses the methodology tools to study human genetic diseases; he has acquired knowledge on the heredity mechanisms in man, on the problems concerning the diagnostics of genetic diseases; he acquires the basics on several methods of analysis at the cell and molecular level, with the capacity to apply them properly to biomedical questions. He understands the significance of modern genetics and has acquired analytical instruments within the professional field.

Course contents

Introduction: what is medical genetics - terms and definitions - structure and function, operational concepts - definition and correlation between genotype and phenotype - wild-type and mutant allele - dominant and recessive hereditability of characters. The Human Genome Project and its evolution into the 1000 Genomes project. Pedigree reconstruction and risk evaluation. Symbols of pedigrees, product and sum rules.
Genetic diseases: canonical hereditability modes - autosomal recessive hereditability and clinical examples (cistic fibrosis) - autosomal dominant heritability and clinical examples (acondroplasia) - X-linked hereditability and clinical examples (Duchenne muscular distrophy). Exceptions to Mendelian inheritance: clinical and genetics heterogeneity. Triplettes expansion diseases: Huntington disease - genetic anticipation, premutation, toxicity; X-fragile - role of methylation and X-inactivation. Noncanonical hereditability. Imprinting, uniparental disomy and epigenetics (Angelman and Prader-Willy syndromes) - Mitochondrial inheritance: matrilinearity, polyplasmy (heteroplasmy and homoplasmy), threshold effect - Penetrance and expressivity with clinical examples. 
Chromosomal pathology: structural and numerical aberrations with clinical examples. Trisomy and monosomy of autosomes and sex chromosomes. Balanced and unbalanced translocations: reproductive outcome of the carrier of balanced translocations. Robertsonian translocations: mechanisms and reproductive problems. Techniques of classic and molecular cytogenetics. FISH and its applications: different types of in situ fluorescence hybridization. Comparative Genomics Hybridyzation techniques (CGH), technical aspects and diagnostics applications.
Multifactorial diseases, empyrical risk evaluation. The role of polymorphisms. Studies on twins cohort (concordance and discordance).
Association studies: polymorphic genetic markers. Linkage analysis, LOD score calculation. Recombinant fraction, informative meiosis. Approaches for the search of a disease gene.
Techniques for DNA analyses and mutational screening. PCR, Real-Time PCR and post PCR analyses: restriction, sanger sequencing, southern/northern blot. Massive sequencing (NGS): 454 pyrosequencing, methods, library preparation, sequencing, data interpretation and caveats; Ion Torrent, principles of the technique, advantages and disadvantages. Exome sequencing techniques. MLPA. Microsatellite analysis. Genetics databases: NCBI, Pubmed, Gene, OMIM, dbSNP. Tools for pathogenicity prediction of protein variants: polyphen2 and mutpred. Tools for primer design and validation: primer3. Ensembl and related tools. 

Readings/Bibliography

Thompson & Thompson - Genetica in Medicina. Idelson-Gnocchi editore.
Tobias, Connor, Ferguson-Smith - Fondamenti di Genetica Medica. Pearson ed.

Teaching methods

Lectures with ppt slides. Class exercises.

Assessment methods

Written test with multiple choice and exercises.

Teaching tools

Students will be provided with ppt slides

Office hours

See the website of Giuseppe Gasparre