Ateneo - UPO

The broad topics covered in the course include the molecular evolution of eukaryotic genomes (phylogeny and phylogenetic trees; mutation rates in the human genome; evolution of gene order within the genome); regulation of gene expression in eukaryotes (key regulatory mechanisms and cell-type induction; diseases linked to regulatory mechanisms; dynamics of genomic region accessibility; characteristics of regulatory sequences; functions of enhancers and transcription factors; transcriptional mechanisms responding to stress and developmental processes); epigenetics (epigenetic chromatin modifications; DNA methylation processes in plants and animals); genome editing; cancer genetics (tumor suppressors and oncogenes; molecular basis of tumors; quantitative and multiplexed tumor genomics; tumor heterogeneity; principles of epigenetic therapies; cancer resistance mechanisms in long-lived mammals); and nutrigenetics and nutrigenomics (relationships between polymorphisms and nutrition; genetics and genomics of food intolerances and detoxification; nutrigenomics of dietary fat intake; applied nutrigenetics).

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
Nutrigenomica ed epigenetica: dalla biologia alla clinica, EDRA ed. 2017
Fondamenti di nutrigenomica e nutrigenetica, Zanichelli ed. 2026
Nature Reviews Genetics 2012, 13: 745-753
Nature Review Genetics 2004, 5: 299-310
Nature Reviews Genetics 2011, 12:554-564
Nature Reviews Genetics 2014, 15:453-468
Nature Reviews Genetics 2011, 12:283-293
Nature Reviews Genetics 2018, 19:385-397
Nature Reviews Genetics 2010, 11:204-220
Nature Reviews Genetics 2014, 15:93-106
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
References to other publications on specific topics covered in the course are indicated on the slides made available to students.

This course aims to explore various concepts in genomics and nutrigenomics in depth. The selected topics are characterized by their actual or potential practical applications across various sectors of human and plant genomics. The course provides detailed information on genes and genetic processes, as well as insights into translating knowledge derived from the covered genomic fields—such as genome evolution, gene expression regulation, epigenetics, genome editing, cancer genomics, nutrigenetics, and nutrigenomics—into practical applications. For several topics, links to active websites are provided; these offer additional information and/or enable data analysis based on the datasets hosted on those sites. Consequently, students gain an up-to-date, comprehensive background in key areas of genomics and nutrigenomics, equipping them to address—critically and proactively—various genetic-based issues they may encounter in their professional careers as biologists or nutritional biologists.

Knowledge of qualitative and quantitative genetics, genetic analysis, and molecular genetics, along with a basic understanding of genetic biotechnology, facilitates learning the topics covered in the course.

Teaching format: Lectures accompanied by slides. The course consists of 48 hours of lectures. It also includes seminars delivered by researchers and medical professionals working in the field of nutrition. Course materials, including PDF versions of the scientific reviews discussed during lectures, will be made available via the UPO DIR platform. Interactive teaching methods will also be employed, fostering opportunities for discussion with students. The knowledge gained through the provided teaching materials (slides available on DIR and presented during the course) is sufficient to pass the exams and meet the expected learning outcomes.

The course is structured around the use of various scientific reviews that cover interconnected topics. Lessons are highly informal and interactive, allowing students to ask questions about the material at any point during the session. At the end of each lesson and the beginning of the next, students are encouraged to seek further clarification on any topics they may not have fully grasped, thereby fostering an active approach to learning.
Students with disabilities, Specific Learning Disorders (SLD), or Special Educational Needs (SEN) may request specific services and support tools by contacting the Student Career Development and Services Staff and consulting the dedicated page on the University website: https://uniupo.it/it/servizi/servizi-studenti-disabili-e-dsa
Once they have contacted the University staff, students with disabilities, SLD, or SEN may also contact the course instructor to discuss the specific arrangements for exams and other teaching-related matters.

Exam format: Written; class attendance is strongly recommended. The exam aims to assess students' ability to apply the concepts learned during the course. It consists of a written test comprising multiple-choice questions. The questions cover the entire course syllabus; the time allowed is 2 hours. The written test consists of 31 questions; a perfect score (all correct answers) results in a grade of 30 *cum laude* (the maximum grade, signifying excellence, achieved by demonstrating outstanding proficiency and a flawless performance). One point is deducted for each incorrect or missing answer, down to a minimum passing grade of 18 (indicating that the student has acquired and understood the basic concepts).
Grade breakdown:
30 - 30 *cum laude* (Excellent): Demonstrates impeccable, in-depth knowledge of genomic, nutrigenetic, and nutrigenomic methods. Produces a comprehensive and rigorous exam paper, demonstrating exceptional independent judgment and an excellent ability to make interdisciplinary connections.
27 - 29 (Very Good): Demonstrates in-depth knowledge and a solid ability to analyze and synthesize genomic, nutrigenetic, and nutrigenomic methods. Produces a comprehensive exam paper, demonstrating the ability to establish logical connections.
24 - 26 (Good): Demonstrates a good grasp of fundamental topics, despite some isolated inaccuracies regarding details or more complex connections. The exam paper is well-executed, and the ability to make connections is adequate. 21 - 23 (Fair): Demonstrates knowledge of concepts that is primarily descriptive or based on rote memorization. There is limited ability to apply concepts to case studies or to reframe the questions asked. The exam paper contains a limited number of serious conceptual errors.
19 - 20 (More than sufficient): Demonstrates minimal and fragmentary knowledge of the course content, with clear difficulties in understanding the implications of genomic-nutrigenomic mechanisms and the applications of the methods.
18 (Sufficient): Demonstrates only a basic and essential understanding of the syllabus's core concepts. Answers are underdeveloped, critical thinking is limited, and there are evident difficulties in linking genomic-nutrigenomic processes with the methods used to analyze them.
Any additional information regarding exam procedures and assessment criteria will be provided at the start of the course.

1 Molecular evolution of genomes. Phylogenetic trees; procedures for constructing phylogenetic trees (UPGMA, NJ, MP, and ML methods). Re-evaluation of mutation rates in the human genome: approaches for estimating genome-wide mutation rates; evolution of rate-estimation parameters and re-evaluation of human evolutionary divergence times. Evolutionary dynamics of gene order in eukaryotes: non-random organization of gene order; mechanisms governing gene co-expression and linkage in eukaryotes.
2 Regulation of gene expression in eukaryotes. Main mechanisms of gene expression regulation. Transcriptional programs and pluripotent/differentiated cells. Mutations in regulatory regions and pathological phenotypes. Splicing mutations and diseases. Genome accessibility dynamics: systems used to assess accessibility to genomic regions; factors influencing nucleosome occupancy; variations in chromatin structure. Regulatory sequences: identification methods; relationships between predicted and *in vivo* regulatory sites; influence of binding site structure on transcription. Enhancers: effects of epigenetic modifications on enhancer function; chromosome conformation capture and the influence of three-dimensional conformations on enhancer function. Modes of transcription factor function: mechanisms of direct and indirect transcription factor cooperation; models of enhancer activity; dynamic changes in enhancers during cellular development; synergistic and hierarchical cooperation in enhancer function. Molecular mechanisms of the transcriptional response to stress: transcriptional reprogramming in response to stress; activation and repression of stress-response genes.
3 Epigenetics. Key epigenetic modifications in DNA and histones. Writers and readers. Non-coding RNAs. DNA methylation patterns in plants and animals: de novo methylation in mammals and plants (epigenetic processes in germlines); maintenance of CG methylation patterns in animals and plants, and CHG patterns in plants; active and passive DNA demethylation. Epigenetic regulation of cell differentiation: epigenetic landscape of embryonic stem (ES) cells and modifications during differentiation; chromatin modifiers in pre-implantation embryonic differentiation; chromatin pre-patterning in cell lineage specification; stability of chromatin modifications.
4 Genome editing. Available editing systems (ZFNs, TALENs, CRISPR/Cas9, Prime editing); double-strand break (DSB) repair systems in DNA editing; details of CRISPR/Cas9 mechanism and origin; examples of editing applications in plants; evolution and additional applications of CRISPR/Cas9 in genomic analysis.
5 Cancer genetics. Cancer and the cell cycle; examples of tumors arising from chromosomal rearrangements; tumor suppressor genes and their main functions; retroviruses and viral oncogenes; proto-oncogenes; oncogene activation mechanisms; insights into the molecular basis of oncogenesis. Functional cancer genomics, quantitative and multiplexed approaches: complexity of genetic alterations in cancer; in vivo functional assessment of tumor suppressors, oncogenes, and fusion genes; multiplexed functional analyses. Cancer heterogeneity: genetic evolution in tumors—positive and negative selection, punctuated evolution; bulk and single-cell sequencing; sampling strategies. Approaches to assessing ongoing selection in tumors; cancer evolution patterns and their implications; evolution of genetic resistance to treatments. Epigenetic approaches in cancer: effects of DNA methylation inhibitors (DNMTi) in epigenetic therapies; effects of DNMTi on ERV reactivation; pathways for inducing responses to epigenetic therapy; epigenetic reprogramming of CTLs. Cancer resistance mechanisms in long-lived mammals.
6 Nutrigenomics: Polymorphisms and nutrition (membrane transporters and receptors, signal transduction systems, enzymes and effector proteins, structural proteins); body weight and metabolic/genomic aspects (genes involved in fat metabolism; nutrigenomic response to dietary fat intake; genes involved in carbohydrate metabolism); genetics and genomics of food intolerances (lactose intolerance; gluten intolerance and sensitivity; histamine intolerance); detoxification systems and processes (phases I, II, and III); Applied nutrigenetics: analysis of polymorphisms of nutritional interest (favism, caffeine and vitamin D metabolism); Potential and limitations of nutrigenetics; Applied nutrigenomics.

Knowledge and understanding: A course such as Genomics and Nutrigenomics—characterized by specific, core subject matter—is expected to bring students' knowledge of the discipline in line with international standards, enabling them to understand genetic and genomic issues that impact health and nutritional status. Students will acquire mastery of the theoretical tools needed to interpret genomic processes and will gain command of appropriate scientific terminology.
Applying knowledge and understanding: By the end of the course, students will be able to apply genetic, genomic, and nutrigenomics concepts when assessing various genetic conditions that affect health and nutritional status. They will also be able to recommend appropriate genotyping analyses to help identify underlying genetic issues.
Making judgments: Ability to independently formulate hypotheses regarding the genetic causes of specific phenotypes and to critically discuss the complex relationships between genotype and pathological phenotype.
Communication skills: Ability to communicate course topics clearly and understandably using correct scientific terminology; ability to interact effectively with both medical professionals and potential clients/patients regarding health and nutritional issues with a genetic basis.
Learning skills: Ability to deepen knowledge in the fields of genomics, nutrigenetics, and nutrigenomics by consulting various textbooks and scientific articles, thereby keeping pace with the evolution of the discipline with a critical mindset. Ability to use educational materials for critical and reasoned study.