Human and Molecular Genetics

1. Structure of the genome
Objectives: To know the composition of the genome, the structure of genes, non-coding regions and repeated sequences. Genetic markers. Genetic mapping and physical mapping of the human genome, the Human Genome Project and genome sequencing, exome sequencing and variant evaluation.

2. Mapping disease genes and DNA polymorphism.
Objectives: To know the general principles of approaches used for mapping disease genes by identifying genetic markers and linkage analysis. Know the concepts of haplotype and linkage disequilibrium, the peculiarities of DNA polymorphisms: RLFPs, minisatellites (VNTRs), microsatellites (STRs), SNPs and illustrate their use as genetic markers.

3. Karyotype
Objectives: learn about human chromosome arrangement, chromosome structure and principles for karyotype analysis. Describe karyotype alterations: aneuploidies, structural alterations and polyploidies. Know the application of classical and molecular cytogenetic techniques (FISH and CGHArray). Describe the mechanisms of generation of chromosomal mosaicisms. Illustrate the characteristics of genomic diseases and mechanisms related to Copy Number Variations (CNVs). Illustrate the main indications for prenatal cytogenetic diagnosis and describe techniques (invasive diagnosis and NIPT).

4. Mendelian Diseases.
Objectives: learn about Mendelian transmission patterns of inherited traits, interpret family trees, calculating the risk of transmission. Describe the main exceptions of Mendelian inheritance (de novo mutations, incomplete penetrance, variable expressivity and germline mosaicism). Explain the concepts of allelic and genetic heterogeneity. Describe the distinguishing features of mitochondrially transmitted diseases.
Describe diseases caused by dynamic mutations and the underlying molecular pathogenetic mechanisms, with reference to diseases exemplifying peculiar molecular defects.
Explain the molecular tests used for diagnosis of Mendelian diseases (Sanger sequencing, Next-generation sequencing, and methylation defect analysis).

5. Epigenetics and Genomic Imprinting
Recognize the characteristics of disease transmission due to defects in genomic imprinting. Illustrate the principles of imprinting regulation, associated pathologies and uniparental disomy.
Illustrate concepts related to epigenetic modifications and interactions of environment on phenotype through epigenetic modifications.
Describe molecular tests to highlight epigenetic defects.

6. Genetic Determination of Sex and X-chromosome Inactivation.
Objectives: Outline the molecular and genetic mechanisms underlying sex determination during embryogenesis. Describe some disease conditions related to errors in sex differentiation and underlying mechanisms.
Illustrate the biological significance of X chromosome inactivation and the molecular mechanisms that determine and regulate it. Describe exceptions to the random inactivation pattern and phenotypic consequences for X-linked disorders.

7. Polygenic and Multifactorial Characters.
Objectives: To be able to distinguish between monofactorial and multifactorial characters and relate it to the existence of discontinuous variability and continuous variability. Illustrate the model that explains the genetic basis of multifactorial characters and know the methods by which the hereditary component (heritability) can be distinguished in humans from the environmental component. Know how to distinguish between multifactorial characters with continuous variability and characters with threshold effect. Describe the threshold model for genetic susceptibility. Describe the mapping of complex characters by association studies.

8. Genes of genetic predisposition to cancer
Objectives: To know the major disease-genes associated with genetic predisposition to cancer and involved in the mechanisms of DNA repair and cell cycle control. To illustrate some examples of genetic predisposition (predisposition to colon cancer, breast cancer, retinoblastoma, and Li Fraumeni syndrome) and describe the role of genetic counseling in families with cancer predisposition.