Human and Molecular Genetics

1. Structure of the genome
Objectives: Know the genome composition, the structure and function of genes, inter/intragenic regions, repeated sequences. Features of genetic markers and their usage in genetic and physical mapping of the human genome. Be familiar with the Human Genome Project and different methods used for genome sequencing.

2. Gene Mapping and DNA polymorphisms in human disease
Objectives: Know the different approaches used for disease genes mapping, through the identification of genetic markers and linkage analysis. Be familiar with the concepts of haplotype and linkage disequilibrium. Know the characteristics of DNA polymorphisms: RLFPs, minisatellites (VNTR), microsatellites (STR), SNPs and to describe their use as genetic markers.

3. Karyotyping
Objectives: know the structure of human chromosomes and the principles for the karyotype analysis. Describe karyotype alterations: aneuploidy, structural changes and polyploidy. Know the application of classical and molecular cytogenetic techniques (FISH and CGHArray). Describe the mechanisms underlying chromosomal mosaicism. Illustrate features of genomic diseases and mechanisms related to Copy Number Variations (CNVs). Explain the main guidelines for prenatal cytogenetic diagnosis and the employed techniques (invasive diagnosis and NIPT).

4. Mendelian diseases
Objectives: know the principles of Mendelian transmission of hereditary characters, explain genealogical trees, calculating the transmission risk. Describe the main exceptions of mendelian inheritance (de novo mutations, reduced penetrance, variable expressivity and germinal mosaicism). Explain the concepts of allelic and genetic heterogeneity. Describe the peculiar transmission features of mitochondrial diseases. Describe the diseases caused by dynamic mutations and the underlying pathogenic molecular maccanisms, with reference to examples of diseases with specific molecular defects. Explain the molecular tests used in diagnosis of Mendelian diseases (Sanger sequencing, Next-generation sequencing and analysis of methylation defects).

5. Epigenetics and genomic Imprinting
Objectives: Recognize the transmission features of diseases caused by defects in genomic imprinting. Explain the principles of imprinting regulation, imprinting related diseases and uniparental disomy.Illustrate concepts related to epigenetic modifications and the interactions of the environment on the phenotype, through epigenetic modifications. Describe molecular tests to highlight epigenetic defects.

6. Genetic determination of sex and X chromosome inactivation
Objectives: Illustrate the molecular and genetic mechanisms underlying sex determination during embryogenesis. Describe pathologies related to errors of sexual differentiation and underlying mechanisms. To illustrate the biological significance of the inactivation of the X chromosome and of the underlying molecular mechanisms. Describe the exceptions to the random inactivation pattern and the phenotypic consequences for X-linked diseases.

7. Polygenic and multifactorial characters
Objectives: Clarify the difference between single-factor and multifactorial characters and to relate it to discontinuous and continuous variability. Illustrate the model explaining the genetic basis of multifactorial characters and know the methods allowing to distinguish the hereditary component (heritability) from the environmental component. Being able to distinguish between multifactorial characters with continuous variability and characters with a threshold effect. Describe the threshold model for genetic susceptibility. Describe the mapping of complex characters through association studies.

8. Genetic predisposition to cancer
Objectives: Know the main disease genes associated with genetic predisposition to cancer and involved in the mechanisms of DNA repair and cell cycle control. Explain some examples of genetic predisposition (colon cancers, breast tumors, retinoblastoma predisposition and Li Fraumeni syndrome). Clarify the role of genetic counseling in families with predeposition to tumors.