Ateneo - UPO

Macro subjects proposed during the course are related to molecular evolution of eukaryotic genomes (phylogenesis and phylogenetic trees; human mutation rate; evolution of eukaryotic gene order; evolution of transcription factor binding sites; transcriptome evolution); regulation of gene expression in eukaryotes (main regulatory mechanisms and induction of cellular types; diseases related to regulatory mechanisms; dynamics of genome accessibility; identification and functions of regulatory sequences; function and features of regulatory sequences; enhancer function; transcriptional factors functions; mechanisms driving transcriptional stress responses and development); epigenetics (epigenetic chromatin modifications; DNA methylation patterns in plants and animals; RNA-mediated epigenetic regulation; plant small RNA; exploiting epigenetic variation in plants); genome editing; cancer genetics (onco-suppressor and oncogenes; molecular bases of tumours; quantitative and multiplexed functional cancer genomics; heterogeneity in cancer; principles of epigenetic therapy; mechanisms of cancer resistance in long- lived mammals).

Genetica, Binelli e Ghisotti, EdiSes, ed. 2018
Genetica, Pierce, Zanichelli, ed. 2016
Korf e Irons, Genetica e genomica umane, edi-ermes, ed. 2015
Principi di genetica, Snustad D.P., Simmons M.J., EdiSes, ed. 2014
Nature Reviews Genetics 2012, 13: 745-753
Nature Review Genetics 2004, 5: 299-310
Nature Review Genetics 2014, 15:221-233
Nature Reviews Genetics 2014, 15:734-748
Nature Reviews Genetics 2011, 12:554-564
Nature Reviews Genetics 2014, 15:453-468
Nature Reviews Genetics 2011, 12:283-293
Nature Reviews Genetics 2012, 13:613-626
Nature Reviews Genetics 2018, 19:385-397
Nature Reviews Genetics 2010, 11:830-842
Nature Reviews Genetics 2010, 11:204-220
Nature Reviews Genetics 2015, 16:71-84
Nature Reviews Genetics 2014, 15:93-106
Nature Reviews Mol Cell Biol 2015, 16:727-741
Nature Reviews Mol Cell Biol 2017, 18:563-575
Nature Reviews Genetics 2018, 19:741-755
Nature Reviews Genetics 2019, 20:404-41
Nature Reviews Genetics 2019, 19:151-161
Nature Reviews Cancer 2018, 18:433-441
Other publications referred to specific topics have been reported on the slides which have been made available to students

Teaching purpose is to deepen several concepts more generally taught in the Genetics I course. Selected topics are characterized for being subjects (or for potentially having) of practical applications in several sectors of human, animal and plant genetics. During the course, detailed information are provided about genes and genetics processes, as well as indications about the transfer to application sectors of knowledge derived from the taught genetics topics (genomes evolution, gene expression regulation, epigenetics, genome editing, cancer genomics). Information about active web sites have been provided for several of the lessons topics, from which additional information can be derived and/or making possible data analysis with those already present in the web site databases. Therefore, the student is provided with a up to date and deep background about important sectors of genetics, to allow her/him to deal with different genetics-related problem, that she/he could meet during his biologist profession, in a critical and proactive behavior.

Knowledge of qualitative and quantitative genetics, genetic analysis, molecular genetics, biotechnology, will favour understanding of the course topics

Teaching procedure: traditional with PowerPoint slides. The course is organized in 48 hours of frontal lessons. Frontal lessons will be carried out by projection of PowerPoint slides. Teaching materials of the course, as well as a pdf copy of the scientific reviews used during the course, will be made available through the UPO DIR platform.

Course organization involves the utilization of several scientific reviews, where topics slightly overlapping are frequently present; this allow, together with interaction with the students, to verify whether topics previously discussed are well fixed. Lessons are informal and interactive, so that students can enquire about lesson topics during every step of the lesson. At the end of each lesson, students are allowed to ask for additional explanations about eventually poorly understood topics.
Students with physical disabilities, Learning Disabilities or Special Education Needs can request specific services and tools via the Staff Sviluppo e Coordinamento Carriere e Servizi alle Studentesse e agli Studenti, consulting the University webpage: https://www.uniupo.it/en/services/services-students-physical-or-learning-disabilities Students with disabilities, learning disabilities or special education needs, once they have contacted the University Staff, can refer to the tutor in charge of the course to define the examination modalities, concerning academic aspects.

Examination procedure: written test. Lessons attendance is strongly suggested. Examination intends to evaluate skills of the student in applying concepts learned during the course. Examination is a written test that will include questions with multiple answers, and some few open questions. Questions will cover all the topics of the course, available time is 2 hours. Possible additional information about examination procedures will be
described at the beginning of the course.

• 1 Genomes molecular evolution. Phylogenetic trees; procedures to build phylogenetic trees (UPGMA, NJ, MP, ML metods). Revising the human mutation rate: approaches to estimate genome mutation rates; evolution of the estimation parameters of evolution rate and revision of evolutionary divergences in humans. Evolutionary dynamics of Eukaryotic gene order: non-random organization of gene order; mechanisms governing co- expression and linkage in Eukaryotic genes. Evolution of transcription factor binding sites: conservation and divergence in the binding sites; mechanisms generating divergences in the binding sites. Evolutionary dynamics of transcriptomes: evolution of gene expression level and splicing; relationships amomg transcriptome evolution and organisms/tissues/sex; regulatory elements in transcriptome evolution.
• 2 Regulation of Eukaryotic gene expression. Main mechanisms of gene expression regulation. Transcriptional programs and pluripotent/differentiated cells. Mutations in regulatory regions and pathological phenotypes. Mutations in splicing and related pathology. Dynamics of genome accessibility: procedure used to assess accessibility to genomic regions; factors affecting nucleosome occupancy; variations in chromatin structure related to positions, temperature, DNA replication. Regulatory sequences: approaches for their identification; relationships among predicted and in vivo regulatory binding sites; how binding sites structure affect transcription. Enhancer: effects of epigenetic modifications on enhancer functions; chromosome conformation capture and effects of tridimensional conformations on enhancer functions. How transcription factors work: mechanisms of direct and indirect mechanisms of transcription factor cooperativity; enhancers activity models; enhancers dynamic changes during progression of cellular development; synergic and hierarchical cooperation in enhancer function. Molecular mechanisms of stress transcriptional response: transcriptional reprogramming in stress response; activation and repression of genes in esponse to stress. Plant transcriptional regulation: gene expression regulation during transition to flowering.
• 3 Epigenetics. Main epigenetic modifications in DNA and histones. Writers and readers. Non-coding RNAs. DNA methylation patterns in plant and animals: de novo methylation in mammals and plants (epigenetic processes in the germinal lineages); maintaining CG methylation patterns in animals and plants and CHG in plants; active and passive DNA demethylation. RNA-mediated epigenetic regulation of gene expression: small-RNA guided DNA methylation in plants and yeast. Epigenetic regulation of cellular differentiation: epigenetic landscape of embryonic stem (ES) cells and differentiation-related modifications; chromatin modifications during embryo pre-implantation development; chromatin pre-patterning for lineage specification; stability of chromatin modifications. Plant small RNAs: mechanisms of small RNAs diversification; biogenesis of primary and secondary small RNAs; small‑RNA modifications and degradation; small-RNA-mediated effects (paramutation, roles during gametogenesis). Exploiting epigenetic
variation for crop improvement: epigenetic patterns distribution in plant genomes; natural and induced epigenetic variation (epigenetic variation in crosses, polyploids, culture tissues and the mantled phenotype in the oil palms).
• 4 Genome editing. Available editing systems (ZFNs, TALENs, CRISPR/CAS9); DSB repairing pathways in DNA editing; details about how CRISPR/CAS9 works and its origin; examples of CRISPR/CAS9 applications in plants; evolution and additional applications of CRISPR/CAS9 in genomic analyses.
• 5 Cancer genetics. Cancer and cell cycle; examples of tumours originated from chromosomal rearrangements; onco-suppressors and their main functions; retroviruses and viral oncogenes; proto-oncogenes; oncogenes activating mechanisms; some indications on oncogenesis molecular bases. Cancer functional genomics, quantitative and multiplexed approaches: complexity of cancer genetic alterations; gene targeting and conditional inducible expression; in vivo functional evaluation of tumour suppressors, oncogenes and fusion genes; multiplexed functional analyses. Heterogeneity in cancer: genetic evolution in tumours: positive, negative, punctuated evolution, bulk- and single-cell sequencing, sampling; approaches to verify selection in tumours; cancer pattern evolution and implications; evolution of resistance to treatments. Epigenetic approaches in cancer: effects of DNA
methylation inhibitors (DNMTi) in epigenetic therapies; effects of DNMTi on ERVs reactivation; epigenetic therapy response pathways; CTL epigenetic reprogramming. Mechanisms of cancer resistance in longlived mammals: resistance mechanisms dependent from replicative senescence and slow cell proliferation; mechanisms of cancer resistance in small- and large-bodies long-lived mammals.

Knowledge and understanding: it is expected that a Genetic II course, characterized by several specific and characterizing topics, the obtained specific knowledge level will be in agreement with International standards. This will allow the student to deal with genetic problems in the human/animal and plant sectors.