Master Degree in WBH
General information, please read carefully.
The lessons are live (not streaming), recordings will be available on this webpage later on.
1) Suggested Textbooks: a)"Genetica. Principi di analisi formale", by Anthony Griffiths (Zanichelli) as the italian translation of the 12th American Edition of the original “Introduction to Genetic Analysis” (Freeman and Company)
b) Eserciziario di Genetica con guida alla soluzione. Daniela Ghisotti, Luca Ferrari. Ed. Piccin. (Exercises book. Ghisotti: no equivalent in English)
2) Types of lessons: 5 credits (40 hours) explicative lessons (frontal)
1 credit (12 hours), exercises
3) The program: The detailed program and calendar of lessons are reported in this webpage. In case of changes in the program through the years, students of past years should update their study based on the most recent program carried out by the professor.
4) Reception of students: There is not any specific time or day for reception. Students may book an appointment by writing directly to the professor, using an institutional (…@unipi.it) e-mail address, at the e-mail address: firstname.lastname@example.org
Any e-mail coming from a non-institutional address (e.g. ...@google.com …@yahoo.com… etc) are filtered by the Anti-spam, and not read.
5) The exam: At the exam (written) the student may carry for themselves only these few things:
1) pen (blue/black)
2) paper (for raw calculations)
3) calculators (allowed)
4) Identity card
5) Laptop (PC/MAC). Recommended. The device must be full charged for a 2-hours of continuous work, and already connected with the exam’s room through WiFi. The written exam is run by the administration of GoogleForms.
6) Tablets could be an alternative to Laptop, but they must have a large screen (at least 10”), a vertical stand, and a regular keyboard. Horizontal displays are not allowed. Vertical displays are mandatory.
6) More on the exam: Follow this link for more information on the final exam: risultati
Copying, consulting webpages different than those administered during the exam (GoogleForms), or talking with other people (inside or outside the exam’s room), is not allowed during the exam. The student will be dismissed by the exam if there will be evidence of any of these infractions.
Planned calendar for year 2022-2023
The official program will be also placed here:
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HOW TO REACH ROOM X:
The address is Via Derna 1, second floor.
This is the video how-to-reach ROOM X.
Academic year 2022-2023, calendar.
Introduction to the course.
Pills of calculation of the probabilities. Introduction to the chi-square test.
Mendel’s life. Careful planning of the experiments, Mendel’s experiments.
Mendel’s first law.
Seven dominant and recessive traits, Mendel’s experiments proving the first and the second law of inheritance.
Mendel’s second law. Definitions of genotype, phenotype, alleles, genes, homozygotes, hybrids, heterozygotes.
Test-cross. Molecular interpretation of what are the variant alleles. Chi-square test proving the divergence between the expected and the observed results. Mendel’s laws in pedigrees. Autosomal dominant and recessive traits in pedigrees. Exercises related to pedigrees.
Phenylketonuria. Inbreeding for recessive traits. Dominant traits. Achondroplastic dwarfism. Marfan Syndrome. Exadactyly, brachydactyly, piebaldism. Incomplete penetrance, variable expressiveness, incomplete penetrance + variable expressiveness. Huntington Disease (Chorea) as a model of variable penetrance (penetrance varying with the age). Other examples: neurofibromatosis. Exercises with pedigrees.
12h30 17h30 10 NobES2 (in substitution of Prof. Cerase)
Slides: set 3
Recording of lessons 4 and 5: part1 ; part2 (English audio only); part3 (English audio only); part4. Download. Part2 and part3 need to be fixed (only audio is available). Please use these videos (part2.mp4 and part3.mp4) with the Italian audio, but it has the same exercise of part2 and part3. So you can compensate by watching the video in Italian, and eventually listening the reply (audio solo) in English. Sorry for this technical problem: part1 ; part2 (both in Italian).
More exercises with the pedigrees to practice with Mendel’s first and second laws. Mendel’s study with two characters. Dihybrids and the Mendel’s third law (the independent segregation). The ratio 9:3:3:1 in F2, following dihybrids of F1. Punnet’s square. Test cross of a dihybrid. Application of the chi-square test to Mendel’s experiments. Exercises to practice with Mendel’s third law.
Inferring parents’ genotypes according to the kind of offspring.
Exploiting the acquired knowledge: synthesis of pure lines. Hybrids and the virescence of the hybrids.
Fraction of hybrids according to the number of generations following self-pollination.
DNA, structure, and replication. The basic chemistry of the DNA. Nucleosides, nucleotides. Deoxynucleosides, deoxynucleotides. Chargaff’s rule. The discovery of the double helix. Basic characteristics of the DNA double helix.
Replication: Cairns’s experiments and the discovery of the “replication bubble”. The origin of replication in prokaryotes and in eukaryotes.
The origin of replication and the replisome in prokaryotes and in eukaryotes. The chemistry of DNA replication. The elongation. Synthesis of the new strand using the parental strand as template. Polymerisation in direction 5’>3’. Release of pyrophosphate and thermodynamics of the reaction. Different types of DNA polymerizations (prokaryotes) with different processivity and different exonuclease activities. The proof reading activity, reducing the error rate. A natural source of errors: the immino and enolic forms of DNA bases. Leading and lagging strand. RNA primase, the Okazaki’s fragments, the role of DNA ligase.
Replication of telomers, the 3’ protruding end and its replication. The role of telomerase. Cells expressing or not expressing telomerase. The machinery allowing the replication of telomeres without shortening. The structure of the telomers, the role of Werner helicase. Relation between telomerase expression and aging or cancer.
Slides: set 4
The dimension of biological molecules. Size of DNA. The discovery of histones. Types of histones. The nucleosome.
The chromatin has the shape of a pearl necklace. Structure of the nucleosome. The 30nm fiber. The scaffold, the 300nm loops.
The replication of the nucleosome, maintaining the epigenetic signals.
An overview of the human genome. Differences between nuclear and mitochondrial DNA.
The human chromosomes, size, dimensions, length. Visualization at the optical and electron microscopy. G-banding and Q-banding. The mitosis. The phases of the cell cycle. The phases of mitosis.
A molecular view of the homolog chromosomes. A molecular view of the alleles. A molecular view of aploidy and diploidy.
The chromosome theory of inheritance (by Morgan). Placing genes on chromosomes. Explaining the third Mendel’s law with the formation of gametes after meiosis. The “coupling”: genes genetically associated.
Evoking the crossing-over in the context of the chromosomal theory of inheritance (by Morgan again). The sub-phases of meiosis, in particular the subphases of the Prophase I. Leptotene, Zygotene, Pachitene, Diplotene.
The formation of the synaptonemal complex. Sister chromatids and recombinant chromatids. Ploidy and the amount of DNA, during the meiotic cycles. Genes linked according to the chromosomal theory of inheritance.
Slides: set 7
Recording of lesson 10 , download
Various types of life cycles, according to the phases of the life in aploid or diploid state. Examples of mammals, plants, fungi.
The ascomycetes, the ascospores of Neurospora crassa as a model for the study of meiosis.
The Hollidays’s junction or intermediate of the crossing over. Models of crossing overs. Formation of heteroduplex DNA and gene conversion.
Linkage mapping: calculation of the map distance between two genetic loci. Drosopila melanogaster with vestigial/long wings and dark/grey body as model for understanding the haplotype “cis” or “trans”. Recognizing the “parentals” and the “recombinants” and observing the number of offspring with the 4 combinations. The description of the “cis” and “trans” (in repulsion) gametic phase (haplotypes), in agreement with the chromosomal theory of inheritance.
Calculation of the map distance using the % of recombinants (expressed as centiMorgan, cM, or map units, um).
Exercises on two-point crosses with genes in linkage.
Calculation of the map distance and how to understand the “cis” “trans” gametic phase (haplotype).
More on the chromosomal theory of the inheritance.
Three-point crosses. Learning how to map 3 genes and calculate their relative genetic distance. Drawing simple genetic maps according to Sturtevant’s method.
More exercises on 3-points crosses.
Slides: set 8
Autosome and sex chromosomes. Sex determination in short. X and Y chromosomes with the homologous region (the pseudo-autosomal region).
Crosses in X-linked recessive traits (example of red eye in Drosophila). Pedigree in X-linked recessive traits: daltonism, Duchenne’s muscular dystrophy, hemophilia.
Exercises on X-linked inheritance.
26 oct 2022 wed 10h30 12h30 28 NobES2
Slides: set 9
Exercises on X-linked inheritance.
Examples of X-dominance inheritance. The X-inactivation (lyonization). Examples and exercises..
Mapping genes on X-chromosomes. Two-points/three point crosses.
Extranuclear inheritance. The study of human evolution through the study of mitochondrial DNA.
Allelic and Gene interactions. The bases of dominance and recessivity.
Beadle and Tatum’s experiments on N. crassa.
Auxtrophic and prototrophic spores. The nutritional deficient mutants.
The one gene = one enzyme hypothesis.
Test of complementation.
Complementation in diploid and the bases of dominance in the metabolic pathways due to enzymatic deficiencies.
The “inborn errors of the metabolism”.
Dominance for haploinsufficiency. Example.
Negative dominance. Examples.
Dominance with “gain of function”. Examples.
Incomplete dominance. Allelic series. The example of codominance: the ABO blood group and its inheritance. Exercises.
According to the level of observations, hemoglobinopathies (like sickle cells anemia) can show dominance, codominance, incomplete dominance.
Letal alleles and the segregation at the crossings.
Two loci interacting. The example of the Coral Snake. Complementation in diploids. Complementation in families. Complementation in cell lines.
Segregation and phenotypes when two loci are in the same biologic pathway. Segregation 9:7
Recessive and dominant epistasis. Segregations 9:3:4 and 12:3:1. Predicting the offspring according to specific model of inheritance.
Suppression. Two mutations suppressing each other, with associated phenotypes for both (simple suppression). Segregation 13:3
Two mutations suppressing each other, with associated phenotype only for one of them. Segregation 10:6
Two interacting loci with recessive lethality: segregation 9:3:3
1 nov 2022 tue Holiday
Recording of lesson 16: part 1 ; download
Multi-loci phenotypes and quantitative-trait loci (QTL). Causes of QTL: allelic series. The example of the erythrocytic acidic phosphatase.
A simple mathematical model of inheritance of QTL based on 3 loci, each biallelic. Rules of the multi-loci QTL.
Slides: set 10
The regulation of gene expression. The work of Jacob and Monod.
The lac operon. The creation of partial diploids of E. coli.
Various experiments on partial diploids and on mutants of the lac operon in E. coli.
Exercises on mutants of the lac operon.
Polar mutations of the lac operon.
Repressor by catabolite. cAMP and CAP protein.
The operon arabinose. The repressor and the AraC protein.
Repressor in Tryptophan operon.
Slides: set 11
The attenuation as another mechanism of regulation of gene transcription in prokaryotes.
The concept of “regulon”, an example: the regulon Galactose (Saccharomyces cerevisiae).
Complex interactions between epigenetic signals (i.e. methyl-Cytosines) and chromatin regulation through multiproteic complexes.
The SWI/SNF complex.
The remodeling of the chromatin. Example of GCN5 and nucleosome as powerful modulators.
Example of interferon beta.
Aging and loss of the “epigenetic memory”.
Basics of the population genetics. Is a given population at the Hardy and Weinberg equilibrium? What is the Equilibrium of Hardy and Weinberg.
Conditions for the HWE.
11 nov 2022 fri 13h30 15h30 38 NobES2
Recording of lessons 19: part 1 ; download
Exercises on Hardy-Weinberg Equilibrium.
Effects of natural selection and fitness on the allele frequencies in populations.
Random genetic drift.
New mutations, natural selection, and genetic drift.
Slides: set 12
The anatomy of a eukaryote gene.
Enhancer, promoter, minimal promoter, transcription start site, 5’ untranslated region (5’UTR), first coding codon (AUG, methionine), exons, introns, 3’ untranslated region (3’UTR), polyadenylation signal.
Coding sequence (CDS), Open Reading Frame (ORF).
Mutations occurring in the above-mentioned regions and possible consequences.
Slides: set 13
The relationship between mutations and biologic effects (part I). According to the anatomy of the eukaryotic genes we are presenting a series of examples (taken from the literature) aimed to help the understanding how a eukaryotic gene works and what are the possible effects when a mutation hits specific regions of a gene.
Mutations within the coding sequence.
Mutations within 5’ UTRs.
Mutations within promoters.
Mutations within the enhancer.
Errors of the splicing.
Recording of lessons 22: part 1 ; download
The relationship between mutations and biologic effects (part 2). According to the anatomy of the eukaryotic genes we are presenting a series of examples (taken from the literature) aimed to help the understanding how a eukaryotic gene works and what are the possible effects when a mutation hits specific regions of a gene.
Mutations within introns and errors of the splicing.
Slides: set 14
Recording of lessons 23: part 1 ; download
Large scale mutations (chromosomal mutations). Difference between euploidy and aneuploidy.
Examples in nature of monoploids. What about crossing different species ? (Example of Raphanobrassica). Sterile and viable hybrids. Autopolypolids. Formation of new species.
How polyploidy can occur in nature. How polyploidy can be induced artificially. Example of the wheat (alloexaploidy).
Why triploids are sterile. Triploidy in humans.
How aneuploidies can occur.
Recording of lessons 24: part 1 ; download
Aneuploidy of sex chromosomes.
Mechanisms of gene dosage according to the number of sex chromosomes.
How aneuploidies of sex chromosomes occur.
Aneuploidies of the autosomes.
Down’s, Pateau, Edwards’ syndromes.
Mater-related age-dependent increased risk of Down’s syndrome.
Why the age of the mother is more important that the father’s age?
Examples of trisomies in nature (Datura stramonium). General rules of euploidies and aneuploidies.
Analysis of chromosomes. Fluorescent in situ hybridization at the interphase.
At the metaphase: G and Q chromosome banding.
The possible shapes of chromosomes.
Recording of lessons 25: part 1 ; download
mutations in the structure of chromosomes.
Germline mutations (mostly occurring during gametogenesis): interstitial deletions. Mechanisms and examples (including Cri-du-Chat and Wolf-Hirschorn syndromes).
Heterozygotes carrying a small interstitial deletions: pairing of the chromosomes at the meiosis and related gametes.
Visualization of interstitial deletions in polythenic chromosomes of insects (D. melanogaster). Mapping of genes exploiting the banding of the polythenic chromosomes (Muller’s work).
Other germline structural mutations: tandem duplications. Mechanisms (unequal crossing-over), some examples (Williams’ syndrome and others from literature).
Tandem duplications and the evolution of genetic loci. The example of the globing genes (locus alpha and locus beta).
Segmental duplications throughout the genomes. Mechanisms (whole genome duplications and divergence).
Other germline structural mutations: peri- and para- centric inversions. Phenotypic effect and the effects on the pairing at the meiosis.
Recording of lessons 26: part 1 ; download
Other germline structural mutations: reciprocal translocations. Balanced and unbalanced. Phenotypes associated with balanced translocations.
Effects of heterozygotes carrying balanced translocations, effects on the pairing on the homologous chromosomes. Various types of segregations and their effects at meiosis I.
Chromosomal mutations at somatic level. Mechanisms and phenotypic effects. Deletions, Interstistial deletions, duplications, inversions, translocations.
Chromosomal aberrations, including acentric fragments, rings, dicentrics.
The position effect (discovered by Muller in the variegated eye of Drosophila. Carcinogenesis related with chromosomal translocations (with position effect or the creation of chimeric genes). The examples of Burkitt’s lymphoma and the myeloid chronic leukemia.
END OF THE COURSE
Recording of lessons 27: part 1 (present soon) ; download
In this extra lesson we are going to show an example of the exam.