Academic Year 2017/2018
- Docente: Giuseppe Gasparre
- Credits: 2
- SSD: MED/03
- Language: Italian
- 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