Molecular diagnostic in genetic diseases (2012/2013)

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Course code
Name of lecturer
Cristina Bombieri
Cristina Bombieri
Number of ECTS credits allocated
Academic sector
Language of instruction
II semestre dal Mar 4, 2013 al Jun 14, 2013.

Lesson timetable

Learning outcomes

The course aims to provide the proper knowledge of medical genetics for the understanding of human diseases and of advanced technologies and methods used in research and molecular diagnosis of genetic diseases.


- Fundamentals of classical genetics. Mendelian inheritance and atypical inheritance patterns: Mitocondrial inheritance, reduced penetrance, varable expressivity; digenic and triallelic inheritance, incomplete dominance, etc. Mosaicism. X chromosome inactivation.
- Molecular genetics in medicine. Gene and chromosomal mutations, mutation nomenclature. Mutagenesis and DNA repair. Molecular pathology of the gene: biological relevance and effect on the phenotype of mutations, role and action of mutations on genetic diseases, methods for mutation classification as disease-causing. Gain and loss of function mutations, dominance and recessiveness. Genotype-phenotype correlation.
- Diseases due to expansion of unstable repeat sequences (dynamic mutations). Unstable repeat expansion, premutation and full mutation, Sherman's paradox, anticipation, molecular analysis of repeat expansion.
- Cytogenetics: human chomosomes, normal karyotype, parent-of-origin effects, chromosomal polymorphisms and CNV. Imprinting and diseases due to genomic imprinting defect.
- Medical cytogenetics. Chromosomal abnormalities, numerical and structural. Chromosomic syndromes and Genome disorders. Uniparental disomy. Uniparental diploidy: hydatiform moles and ovarian teratomas.
- Bases of human genetics. Human genome organization, gene order on human chromosomes. Structure of eukaryotic genes. Repetitive DNA. DNA polymorphisms: RFLP, SNP, VNTR, minisatellites, microsatellites. Genetic markers, physical and genetic maps. Linkage Disequilibrium.
- Mendelian disease gene identification. Positional and functional cloning. Linkage analysis, human gene mapping, sequencing. Mutation identification.
- Medical genetics. Genetic and hereditary diseases. Examples of single-gene diseases. Preparation and interpretation of pedigrees. Modifier genes and complexity in single-gene disorders. Heteroplasmy and mitochondrial diseases.
- Methods of nucleic acid molecular analysis. PCR, real-time-PCR, electrophoresis, Sanger sequencing, hybridization, reverse dot blot, oligonucleotide ligation assay (OLA). Molecular diagnosis of genetic diseases, direct and indirect mutation analysis, diagnosis by linkage analysis.
- Methods of chromosome analysis. Banding methods, karyotype analysis. Fluorescence in Situ hybridization (FISH), FISH painting, SKY-FISH. Array CGH.
- Genetic testing. Diagnostic, presymptomatic, susceptibility, heterozygote identification, and pharmacogenetic tests. Applications and quality controls of genetic testing. Determination of genetic risks. Bayesian analysis. Consanguinity. Pre and post-natal diagnosis, population genetic screening, neonatal screening. Individual identification, paternity testing. Total and partial chimerism after bone marrow transplantation.
- Genetic variation in individuals and populations. Mutation and polymorphism. The Hardy-Weinberg law, allele and genotype frequency calculation.
- The inheritance of multifactorial traits. Genetics of common disorders with complex inheritance, genetic and environmental factors, qualitative and quantitative traits, genetic predisposition to common diseases.
- Identification of genetic factors in complex diseases. Segregation analysis. Mapping of complex traits. Familial and twin studies, Allelic Identity by State (IBS) or by Descendant (IBD). Parametric and Non-Parametric Linkage. Linkage and association analyses. Candidate gene studies. Transmission Disequilibrium Test (TDT). SNP, haplotype and genome wide association studies (GWAS).
- From human genome project to HapMap, 1000 Genome Project, Biological Encode Project , HGV project
- Pharmacogenetics. Individual variation of drug response. Genes and polymorphisms of drug metabolism and mechanism of drug action. Molecular diagnostics of pharmacogenetic traits.
- Cancer genetics. Cancer as genetic, somatic and multifactorial disease, hereditary and sporadic cancers, Two-Hits model. Classification and characterization of cancer genes (oncogenes, gatekeeper and caretaker tumor soppressor genes). Loss of heterozygosity (LOH), microsatellite instability (MIN).

- R.L. Nussbaum, R.R. McInnes, H.F. Willard. Thompson & Thompson Genetics in Medicine. 7th ed. Saunders Elsevier 2007 (English language).
- Andrew Read and Dian Donnai. Genetica Clinica. I ed. Zanichelli 2007 (Italian language) or the new edition: “Andrew Read and Dian Donnai. New Clinical Genetics. 2nd ed. Scion Publishing Ltd. 2010” (English language).
- G. Neri e M. Genuardi. Genetica Umana e Medica. II Ed. Elsevier Masson 2010 (Italian language).

- To deepen the proposed topics:
Tom Strachan and Andrew Read. Human Molecular Genetics. 4th ed. Garland Science - Taylor and Francis Group, 2010 (English language).

Possible updatings or communications will be available during the course on the webpage dedicated to this course at “e-learning portal of University of Verona”.

Assessment methods and criteria

Oral examination