PROGRAMMA DEL CORSO DI GENETICA
SCIENZE NATURALI
a.a. 2003-2004
prof. S. Presciuttini
C/o Centro Retrovirus
Dip. Patologia Sperimentale - Università of Pisa
S.S. Abetone e Brennero 2
56127, Pisa, Italy
tel. + 39 050 2213797
sprex@biomed.unipi.it
PARTE I) BIOLOGIA MOLECOLARE DEL GENE
I.1 L’unità della vita a livello molecolare
1. Four classes of macromolecules - 2. Functions of macromolecules - 3. Chemical composition of
biomolecules - 4. Monomers - 5. Monomers to polymers - 6. Sucrose, glucose, fructose - 7. Functional
groups defined - 9. Twenty aminoacids and five nucleotides - 10. Introducing metabolism - 11. Polymers,
monomers, metabolites - 12. Chemical reactions in cells - 13. Introducing enzymes - 14. The active site 15. The “Lock-and-key” metaphor - 16. Additional components of enzymes - 17. The active site of
carboxypeptidase. - 18. Metabolic pathways - 19. Metabolic pathways of phenylalanine in human - 20.
Enzymes build everything - 21. Enzymes are proteins - 22. The sequence of aminoacids - 23. Triplets of
nucleotides - 24. The genetic code - 25. Codons and aminoacids - 26. Information flux in a living cell -
I.2 Sviluppo storico della genetica
1. The laws of inheritance and the discovery of chromosomes - 2. Mendel's principles - 3. Where do
genes reside? - 4. The word GENETICS is formulated - 5. Genes are lined-up on chromosomes - 6.
Genes may cause quantitative variation - 7. The first mutagenic agent - 8. An early hypothesis on the
function of genes - 9. The Beadle and Tatum experiment - 10. The life cycle of a fungus - 11. Auxotroph
mutants - 12. Inferring a metabolic pathway - 13. The one-gene one-enzyme hypothesis - 14. Which
macromolecule carries the genes? - 15. An experiment with bacteriophages - 16. 32P and 35S - 17. DNA
is the genetic material
I.3 DNA, geni e genomi
1. The Building Blocks of DNA - 2. The four nucleotides - 3. The double helix - 4. Strand polarity - 5.
Base pairing - 6. DNA forms giant molecules - 7. How much DNA per genome? - 8. Genome sizes - 9.
Lenght of a DNA molecule - 10. The nucleoid - 11. Eukaryotic Nuclear Genomes - 12. DNA in
interphase - 13. The 30 nm fibre - 14. Compacting factors - 15. The average lenght of coding regions - 16.
A “gene” is not only coding sequence - 17. Introns and exons - 18. Schematic gene structure - 19.
Number of introns-exons per gene - 20. Average gene length - 21. Genomes and genes - 22. Most
eukaryotic DNA does not include genes - 23. Comparing gene densities - 24. A small fraction of total
eukaryotic DNA is coding - 25. Coding sequences are needles in the haystack -
I.4 Trascrizione e traduzione
1. Genes and RNA - 2. Properties of RNA - 3. Uracil instead of thymine - 4. Classes of RNA - 5.
Informational RNAs - 6. Functional RNAs - 7. One DNA strand is the template - 8. 5’?3’ - 9.
Transcription in action - 10. RNA Polymerases - 11. Three stages of transcription - 12. INITIATION - 13.
The promoter - 14. The TATA box - 15. RNA polymerase in bacteria - 16. The s factor - 17. Structure of
a bacterial RNA polymerase - 18. ELONGATION - 19. TERMINATION - 20. RNA Processing in
Eukaryotes - 21. The RNA polymerase II holoenzyme - 22. mRNA maturation - 23. Mechanism of exon
splicing - 24. The spliceosome - 25. The translation - 26. Ribosomes are protein factories - 27. The
tRNAs - 28. Chain termination -
I.5 Regolazione della trascrizione
1. The logic of prokaryotic transcriptional regulation - 2. Activators, repressors, effectors - 3. A molecular
switch - 4. Regulation of the Lactose System - 5. Introducing the operon - 6. The metabolism of lactose 7. The gene for the Lac repressor and the lac operator site - 8. The lac operon is regulated by lactose - 9.
The lac repressor - 10. The complex between the lac repressor and the lac operator - 11. A second
mechanism of control - 12. The effect of glucose - 13. cAMP and CAP - 14. CAP binding to DNA-CAP
binding site - 15. The 5’ lac operator control region - 16. The effect of cAMP-ligated CAP - 17. A
summary of the lac operon control -
I.6 La replicazione del DNA
1. DNA Replication - 2. The model of Watson and Crick - 3. Three alternative patterns for DNA
replication - 4. The Meselson-Stahl experiment - 5. Centrifugation of DNA in a cesium chloride (CsCl)
gradient - 6. The proof of the semiconservative model - 7. Harlequin chromosomes - 8. Visualizing sister
chromatids - 9. DNA replication fork - 10. DNA polymerases - 11. DNA polymerases in E. coli - 12.
Prokaryotic origins of replication - 13. A replicating E. coli chromosome - 14. Eukaryotic origins of
replication - 15. Replication bubbles in the fruit fly - 16. Replication bubbles - 17. Priming DNA
synthesis - 18. Leading strand and lagging strand - 19. Discontinuous synthesis - 20. Steps in DNA
synthesis - 21. A comprehensive view of the replication fork - 22. Other DNA-modifying enzymes - 22.
The action of topoisomerases -
PARTE II) I MECCANISMI DELL’EREDITA’ BIOLOGICA
II.1 Ciclo cellulare, mitosi e meiosi
1. Cell Division - 2. Types of cell division - 3. Life cycles of humans, plants, and fungi - 4. G1, S, G2, M
- 5. Mitosis - 6. The four stages of mitosis - 7. Prophase - 8. Metaphase - 9. Metaphase chromosomes - 10.
Anaphase and telophase - 11. Cells in active proliferation - 12. Meiosis: Prophase 1 - 13. Meiosis:
Metaphase I, Anaphase I, and Telophase I - 14. Meiosis I Stages of Trillium erectum - 15. Meiosis 2 - 16.
Meiosis II Stages of Trillium erectum - 17. Comparing mitosis with meiosis -
II.2 Gli esperimenti di Mendel
1. Inheritance Patterns of Individual Genes (1) - 2. Inheritance Patterns of Individual Genes (2) - 3.
Mendel’s experiments - 4. The reasons of a choice - 5. Differences among plant peas - 6. Characters
selected for experiments - 7. Plants differing in one character - 8. Dichotomous phenotypes - 9.
Reciprocal crosses - 10. Monohybrid crosses - 11. Dominance defined - 12. A diagram of Mendel’s
monohybrid experiments - 13. Mendel’s theory - 14. The 1:2:1 ratio - 15. The backcross - 16. Dihybrid
crosses - 17. Yellow/green-round/wrikled seeds - 18. DiHybrid-cross F2 ratios - 19. Visualizing the
9:3:3:1 ratio - 20. The Punnett square - 21. Chi-square analysis of Mendel’s single-plant observations
II.3 Eredità mendeliana nell’uomo; le emoglobinopatie
1. Hemoglobinopathies - 2. Two groups of hemoglobinopathies - 3. Major and minor thalassemia - 4.
Human pedigree symbols - 5. Topic 5 - 6. Autosomal Recessive Disorders (1) - 7. Autosomal Recessive
Disorders (2) - 8. Autosomal Dominant Disorders - 9. X-Linked Recessive Disorders - 10. Hemophilia 11. Complexity of thalassemias - 12. The hemoglobin molecule - 13. A problem of development - 14.
Fetal hemoglobins - 15. Chromosomal locations of globin genes - 16. Organization of globin gene family
in human - 17. Globin genes and hemoglobin molecules - 18. Gene dosage
II.4 Genotipo e fenotipo
1. From Genes to Phenotypes - 2. One-to-many relationship of genes to phenotypes - 3. One-to-many
relationship of phenotypes to genes - 4. The complementation test - 5. Performing the complementation
test - 6. Mutants that complement - 7. The biochemical explanation - 8. Complementation - 9. Interactions
Between the Alleles of One Gene - 10. Incomplete dominance - 11. Codominance - 12. Relativity of
dominance relationships - 13. An anomalous segregation ratio - 14. Letal alleles - 15. What goes wrong in
lethal mutations? - 16. Complex gene interactions in coat color - 17. The A gene - 18. The B gene - 19.
The C gene - 20. The D gene - 21. The S gene - 22. Modifier genes - 23. Penetrance and Expressivity
II.5 La concatenazione e le mappe genetiche
1. An early dihybrid cross - 2. Testing the segregation ratios in the Bateson-Punnett cross - 3.
Comfirmation of coupling in Drosophila - 4. Results of Morgan’s experiment - 5. Repeating the cross - 6.
A hypothesis about coupling - 7. Crossovers - 8. Recombination - 9. Recombination by crossing-over 10. Recombination frequency in Morgan’s crosses - 11. Interpreting linkage data - 12. Sturtevant
approach - 13. The genetic map unit - 14. Linkage groups - 15. An example of linkage map
III) LE MUTAZIONI E IL LORO DESTINO NELLE POPOLAZIONI
III.1 La mutazione genetica
1. Gene and chromosome mutation - 2. Basic terminology - 3. Somatic mutations - 4. Germinal mutations
- 5. Hemophilia - 6. Point mutations: base substitutions - 7. Point mutations: additions/deletions - 8.
Functional consequences of point mutations (1) - 9. Functional consequences of point mutations (2) - 10.
Examples of point mutations - 11. Mutations in non-coding regions - 12. Do mutations arise
spontaneously? - 13. Spontaneous vs induced mutations - 14. Different predictions - 15. The “fluctuation
test” - 16. Results of the fluctuation test - 17. Measuring the mutation rate
III.2 Mutazione spontanea e indotta
1. Mechanisms of Spontaneous Mutation - 2. Errors in DNA replication. - 3. Base mismatches - 4. From
mispairs to mutations - 5. Transitions vs transversions - 6. Frameshift mutations - 7. Spontaneous DNA
lesions - 8. A mutational spectrum - 9. Hot spot mutation sites - 10. Deletions and duplications - 11.
Induced mutations - 12. Spontaneous vs induced mutations - 13. Forward mutation frequencies obtained
with various mutagens in Neurospora - 14. Specificity of mutagens - 15. Still on mutagen specificity - 16.
Mechanisms of mutagenesis - 17. Incorporation of base analogs - 18. Specific mispairing - 19.
Intercalating agents - 20. Base damage and SOS repair - 21. SOS repair and cancerogenicity - 22.
Ultraviolet light - 23. Ionizing radiation - 24. Bulky addition products
III.3 Oncogèni e geni soppressori di tumore; sindromi ereditarie di cancro
1. Relationship between mutagens and carcinogens - 2. AFB1 , UV light, and cancer - 3. The p53 tumorsuppressor gene - 4. How p53 arrests the cell cycle in G1 - 5. p53 and the cell cycle - 6. p53 and
apoptosis - 7. Mutations in tumor suppressor genes are recessive at the cellular level - 8. Oncogenes and
tumor-suppressor genes - 9. The oncogene Ras - 10. Oncogenic Ras mutations - 11. Li-Fraumeni
Syndrome - 12. A typical pedigree of Li-Fraumeni syndrome - 13. Sporadic vs hereditary tumors - 14.
Inherited syndromes of cancer due to germline mutations in tumor suppressor genes
III.4 Tassi di mutazione e tassi di sostituzione; la deriva genetica
1. Mutation Rates - 2. Nucleotide mutation rate - 3. Evolution in a glass - 4. The chemostat - 5.
Fluctuations of mutant strains - 6. Neutral mutations - 7. An example with yeast - 8. Interpreting mutant
fluctuations - 9. Genetic drift - 10. Extinction of genetic variability by genetic drift - 11. Genetic drift over
evolutionary time - 12. The probability of fixation of a neutral allele - 13. The concept of gene
substitution
III.5 Tassi di mutazione nucleotidica e genica; modelli di selezione
1. Estimating nucleotide mutation rate in human - 2. Nachman and Crowell main results - 3. Nachman
and Crowell results (1) - 4. Nachman and Crowell results (2) - 5. Nachman and Crowell results (3) - 6.
Nachman and Crowell results (4) - 7. Mutation rates per gene in humans - 8. Summary of mutation rates
in human - 9. Selection - 10. How selection works - 11. Hardy-Weinberg Equilibrium - 12. How selection
works (2) - 13. Fitness and selection - 14. Change of allele frequency in one generation - 15. Number of
generations required - 16. Selection in complex situations - 17. Testing Hardy-Weiberg equilibrium for
HbA/HbS - 18. HWE in an adult population - 19. Hetrozygote advantage - 20. Equilibrium allele
frequencies for balanced polymorphisms