Genetics

HUMAN GENETICS (BIO/13)
Topic 1 Human genome project: purpose and effects
Topic 2 Human genome organization
Topic 3 Extensions of Mendelian Genetic Analysis: Complete dominance, Incomplete dominance Codominance, Blood groups, multiple alleles, Lethal alleles, The relationships between gene expression and environment (Penetrance, Expressivity Pleotropy)
Topic 4 and 5 Patterns of Single Gene Inheritance: The goals of pedigree analysis and the construction of a pedigree (symbols and rules); the key information helpful for drawing a genetic family history, the basic Mendelian patterns (Autosomal recessive, Autosomal dominant X-linked recessive, X-linked dominant, Y-linked)
Topic 6 and 7 Complications to the basic mendelian pedigree patterns: Pseudo Dominance Reduced Penetrance, Variable expression ,Age of onset, De novo mutation and germline mosaicism, Genetic heterogeneity (allelic heterogeneity in Cystic Fibrosis, locus heterogeneity), Complementation, Digenic inheritance, Non mendelian Inheritance: Mitochondrial Inheritance
Topic 8 Genetic Linkage, Genetic recombination
Topics 9-10 Human genetic variation: DNA mutations, Mutation classification, Effects on proteins , the potential consequences (on gene expression) of the different types of mutation (gain of functions, loss of function), examples of human disease caused by different types of mutation: Cystic Fibrosis, Quantitative and qualitative Hemoglobin disorders (Thalassemia and Sickle Cell anemia), metabolic disorder:PKU.
Topics 11 DNA polymorphisms: RFLP, SNPs, microsatellites and minisatellites
Topic 12-13 Dynamic Mutation: The concept of triplet repeats diseases and the correlation between earlier manifestations of clinical symptoms ('anticipation') and molecular pattern, the classification of diseases due to unstable repeat expansions, Polyglutamine diseases: Huntington's Disease, Fragile X Syndrome, FXTAS and the RNA gain-of-function mode, Myotonic dystrophy (DM)
Topics 14-15 Population genetics Genetic variability in a population: genotypic and allele frequencies. The Hardy-Weinberg law (HWL) of allelic and genotypic frequencies and the Hardy-Weinberg equilibrium (HWE). Factors causing evolution of a population (changes of allelic frequencies over generations) equal to violations of the Hardy-Weinberg postulates
Topics 15-16 Complex Disorders Analysis of genetic principles involved in diseases with multifactorial inheritance: Polygenic Traits and Variation in Phenotype, Additive Model for Polygenic Inheritance, Multifactorial Traits: Polygenic Inheritance and Environmental Effects, Heritability as measure of the Genetic Contribution to Phenotypic Variation, Twin Studies and Multifactorial Traits
Topics 17-18 Mapping genetic disorders. Discussing how geneticists go about discovering the particular genes implicated in disease and the variants they contain that underlie or contribute to human diseases, Association studies (GWAS)
Topic 19 The treatment of genetic disorders

MEDICAL GENETICS (MED/03)
Topic 1 Mitosis, meiosis and Cytogenetics Chromosome behaviour during cell cycle in somatic and germinal cells: haploid and diploid chromosome content during meiosis and mitosis, recombination and crossing-over events and their significance for the genetic variability. Spermatogenesis and oogenesis: a comparison. The Karyotype description: the basic structure and function of chromosomes, the karyotyping procedure (suitable cells, staining procedures, nomenclature ISCN), chromosomal polymorphism.
Topic 2, 3, 4, and 5 Clinical cytogenetics The chromosomal abnormalities in humans and their importance in the phenotype and reproductive risk. Classification of chromosomal anomalies: numerical and structural chromosomal anomalies, concept of balanced and unbalanced conditions.
Aneuploidy involving autosomes, viable autosomal trisomies (chromosome 21, 18 and 13). Aneuploidy involving sex chromosomes (Turner and Klinefelter syndrome). Structural chromosomal anomalies, balanced anomalies (reciprocal and robertsonian translocations, inversion and insertion, how occurs during meiosis and discussion of problems in reproduction), unbalanced anomalies. Clinical indications for postnatal karyotype analysis. The recurrence risks in pregnancy for the principal types of cytogenetic abnormality (trisomies and translocations). Cytogenetic investigation in Prenatal diagnosis: significance and goals of prenatal diagnosis, methods for Prenatal diagnosis and Screening (non-invasive or invasive techniques), indications for prenatal diagnosis by invasive testing. Comparison between the techniques that can be used to identify and clarify chromosome rearrangements. Molecular Cytogenetic techniques: FISH, array-CGH and their use in identifying clinically relevant chromosome abnormalities. The pre- and post-natal applications of cytogenetic investigation.
Topic 6 Clinical cytogenomics Copy number variations: from interindividual genetic variability to disease. The genomic disorders, clinical cases.
Topic 7 CNVs Significance Assessment Flow chart: case studies
Topic 8 Sex determination The genetics of sex determination and the more frequent genetic anomalies associated with incomplete sexual differentiation: the genetic influence in development of the gonads and the importance of the SRY gene in male sex differentiation, sex determination disorders related to genetic defects, genes known to be involved in 46,XY and/or 46,XX gonadal disorders of sex development.
Topic 9 X-linked gene dosage compensation X and Y chromosomes comparison. The importance of X chromosome inactivation in females related to female-male X linked gene dosage compensation: the mechanism leading to X-linked gene silencing related to XIST, random and preferential inactivation of the chromosome X and the impact in heterozygous females. Preferential X-inactivation in presence of chromosome alterations involving X. X-linked genes escaping X inactivation process and its clinical implications.
Topic 10-11 Atypical mechanisms of inheritance: genetic imprinting Atypical Mendelian inheritance pattern involving gene subjected to genomic imprinting. Evidences of genomic imprinting phenomenon. Establishment of imprinting: the epigenetic mechanisms leading to silencing of the imprinted allele trough differential methylation control region, insulators and long non-coding RNA involvement. Mechanisms of diseases in imprinting disorders: Uniparental disomies (UPD), deletions, (epi)genetic defects in imprinted control regions, gene mutations. Imprinting diseases: PraderWilli/Angelman syndromes and Silver Russell/Beckwith-Weidemann syndromes. Multi-locus imprinted defects.
Topic 12 Gene testing and genetic counselling The main classes of gene testing and methods to perform them. The importance of genetic counselling in genetic testing procedures. Genome diversity, the concept of genetic polymorphism and rare variant, how polymorphism can be used in medical practice.
Knowledge and application of the main molecular genetic techniques for gene testing. Concept of direct gene testing and indirect testing (gene tracking). Applications of gene testing: carrier screening, pre-symptomatic testing for predicting adult-onset disorders, diagnosis confirmation of a symptomatic individual.
Topic 13 NGS approaches assesment of Single Nucleotide Variants (SNVs) effect
Topic 14 Principles of molecular diseases: effect of mutations on protein function, examples of Mendelian disorders illustrating mechanism by which mutations produce disease in different classes of proteins (Achondroplasia, Osteogenesi Imperfecta).
Topic 15 Mosaicism in Human Diseases: how a mosaic condition can complicate clinical and molecular diagnosis. Effect position: when the mutation does not affect coding gene sequences.
Topic 16 Understanding the molecular basis of penetrance defects and phenotype variability: When genotype is not predictive of phenotype
Topic 17 The genetic basis of cancer Genes in which mutations cause cancer: oncogenes, tumor suppressor genes (gatekeepers and caretakers genes) Type of genetic alterations responsible for initiating cancer: Activating or gain of function mutations, ectopic or heterochronic mutations, chromosome translocations; loss of function mutations Genomic instability and tumor progression
Topic 18 Sporadic, familiar and hereditary cancer: activated oncogenes in hereditary cancer syndrome: MEN2, Gatekeeper tumor suppressor genes in AD cancer syndromes. The two-hit origin of cancer: the hereditary and sporadic forms of retinoblastoma. The Li-Fraumeni syndrome. Caretaker genes in autosomal dominant cancer syndromes BRCA1 and BRCA2 mutations in familial breast cancer. Familial colon cancer. Counselling and germline mutation testing
Topic 19 Pharmacogenetics and pharmacogenomics: genetic variation, drug response and personalized medicine.