Genetics
Master Degree in WBH
Link to the
results of the final exam (written exam) and procedures for carrying out the
exam
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: stefano.landi@unipi.it
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:
https://unimap.unipi.it/registri/registri.php?ri=9583&tmplt=principale.tpl
–Warning:
video links may not start automatically and in some cases only the audio file
will start.
If
so, it is advisable to click on the link with the right mouse button and save
the file on the PC using “Save destination as”.
Then
use a player to read the MP4 file, VLC player recommended.
90-minute
files are approximately 2GB. Download times vary depending on the network.
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.
28 sept 2022 wed 10h30 12h30 2 NobES2
Slides:
set 1,
and set
2, downloadable
Recording
of lesson
1, and transcript,
download.
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.
30 sept 2022 Fri 13h30 15h30 4 NobES2
Recording
of lesson
2, and transcript,
download.
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.
4 oct 2022 tue 16h00 18h00 6 ROOM X
Recording
of lesson
3 part 1 ; part2
; part3
; part4.
Download.
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.
5 oct 2022 wed 10h30
15h30 8 NobES2
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.
7 oct 2022 fri 13h30 15h30 12 NobES2
Recording
of lessons 6: part1 ; part2
; and transcript,
download.
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.
11 oct 2022 tue 16h00 18h00 14 ROOM
X
Slides: set
4
Recording
of lessons 7: part1 ; part2
; part
3 ; transcript,
download
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.
12 oct 2022 wed 10h30 12h30 16 NobES2
Recording
of lessons 8: part1 ; part2
; part
3 ; transcript,
download
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.
14 oct 2022 fri 13h30 15h30 18 NobES2
Recording
of lessons 9: part1 ; part2
; transcript,
download
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.
18 oct 2022 tue 16h00 18h00 20 ROOM
X
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).
19 oct 2022 wed 10h30 12h30 22 NobES2
Recording of lesson 11: part
1 and part
2 , download
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.
Interference.
More
exercises on 3-points crosses.
21 oct 2022 fri 13h30 15h30 24 NobES2
Slides: set
8
Recording of lesson 12: part
1 and part
2 , download
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.
25 oct 2022 tue 16h00 18h00 26 ROOM
X
26 oct 2022 wed 10h30 12h30 28 NobES2
Slides: set
9
Recording of lessons 13 and 14: part
1 ; part
2 ; part
3 ;
part
4 ; download
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.
Heteroplasmy.
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.
28 oct 2022 fri 13h30 15h30 30 NobES2
Recording of lesson 15: part
1 ; part
2 ; download
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
31 oct 2022 mon This
lesson will not be held
1 nov 2022 tue Holiday
2 nov 2022 wed 10h30 12h30 32 NobES2
Recording of lesson 16: part
1 ; download
tRNA
suppressor.
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.
Exercises.
4 nov 2022 fri 13h30 15h30 34 NobES2
Slides: set
10
Recording of lessons 17: part
1 ; part
2 ; download
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.
8 nov 2022 tue 16h00 18h00 36 ROOM
X
Slides: set 11
Recording of lessons 18: part
1 ; part
2 ; part
3 download
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.
9 nov 2022 wed This
lesson will not be held
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.
15 nov 2022 tue 16h00 18h00 40 ROOM
X
Slides: set
12
Recording of lessons 20: part
1 ; part
2 ; download
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.
16 nov 2022 wed 10h30 12h30 42 NobES2
Slides: set
13
Recording of lessons 21: part
1 ; part
2 ; download
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.
Overlapping
genes.
Mutations
within 5’ UTRs.
Mutations
within promoters.
Mutations
within the enhancer.
Errors of the
splicing.
18 nov 2022 fri 13h30 15h30 44 NobES2
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.
22 nov 2022 tue 16h00 18h00 46 ROOM
X
Slides: set
14
Recording of lessons 23: part
1 ; download
Large scale
mutations (chromosomal mutations). Difference between euploidy and aneuploidy.
Euploidies.
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.
Aneuploidies.
How
aneuploidies can occur.
Turner’s
syndrome.
23 nov 2022 wed 10h30 12h30 48 NobES2
Recording of lessons 24: part
1 ; download
Aneuploidy
of sex chromosomes.
Klinefelter’s
syndrome.
XXY males.
XXX
females.
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.
25 nov 2022 fri 13h30 15h30 50 NobES2
Recording of lessons 25: part
1 ; download
Large scale
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.
29 nov 2022 tue 16h00 18h00 52 ROOM
X
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
30 nov 2022 wed 10h30 12h30 54 NobES2
Recording of lessons 27: part
1 ; download
In this extra
lesson we are going to show an example of the exam.