Portale di Ateneo - En.Unibs.it

- Introduction to the course and contents. Genetics in history. Hemophilia in European and Russian royal families as an example of genetic pathology with personal and historical impact. The fundamental stages of modern genetics. The meiosis and mechanisms underlying genetic variability among individuals. Comparison between mitosis and meiosis. Spermatogenesis and oogenesis and hormonal control. The normal human karyotype and preparation techniques. Bandages of the chromosomes G, Q, R, C. Amniocentesis and villocentesis.

- The pathological karyotype: chromosomal aberrations of number and structure. Aneuploidy and mitotic and meiotic disjunction. Polyploidy, mixoploidy. Examples of aneuploid disorders: Down syndrome, Edward, Patau, Turner and Klinefelter. Structural chromosomal aberrations: deletions, duplications, inversions, ring chromosomes, isochromosomes, reciprocal and non-reciprocal translocations including Robertsonian. Cri du Chat syndrome as an example of deletion syndrome; chronic myeloid leukemia as an example of mutual translocation (bcr-abl). The cytogenetic nomenclature of the main chromosomal aberrations. The FISH technique and the "whole chromosome painting" for the diagnosis of chromosomal aberrations and examples. The DECIPHER database as a collection of clinical association data between chromosomal aberrations and phenotype. The ORPHANET database for the collection of rare disease information.

- Mendel's experiments and laws: monohybrid, dihybrid and trihybrid crossbreeds. Mendelian characters in man: the example of albinism and deafness. Point-like gene mutations. Autosomal recessive mode of transmission. Sickle cell anemia. Cystic fibrosis. Autosomal dominant mode of transmission. Achondroplasia. Marfan syndrome. Neurofibromatosis. X-linked transmission mode. Muscular dystrophies. Color blindness.

- Dynamic mutations. Examples of triplet expansion pathologies: Huntington's Korea, Myotonic Dystrophy, FRAXA. The dominant X-linked inheritance is the example of hypophosphatemia. Non-Mendelian inheritance: the maternal mitochondrial genes. Examples of mitochondrial transmission pathologies. Definition of penetrance and expressiveness. Independent genes, concatenated genes. The SRY gene and the determination of sex. Genetic, gonadal and phenotypic sex. The syndrome of insensitivity to androgens. Exercises and problems on how to transmit human Mendelian characters.

- Examples of prediction of character transmission modes from the pedigree analysis. Calculation of the probability of transmission of Mendelian characters. Continuous and discontinuous phenotypes. Complex, polygenic and multifactorial characters. The example of man's height as an additive model of polygenic inheritance.

- Molecular genetics. The technology and applications of PCR and RT-PCR. The Northern blot. Recombinant DNA: restriction enzymes, plasmid cloning and expression vectors. Reference to the BAC and YAC.

- Genomic and expression libraries. Principles and applications of the Western blot. Immunohistochemistry. Molecular diagnosis of sickle cell anemia by RFLP and Southern blot analysis.

- DNA sequencing: Sanger method. Automatic capillary sequencing. Reading of some pathological electropherograms: the example of papillary renal carcinoma and dental agenesis. Genetic tests. From the pre-test phase to the communication of the result: modality, peculiarity and criticality.