MEDICAL GENETICS AND PHARMACOGENOMICS
GENETICA MEDICA E FARMACOGENOMICA
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Course partially taught in a foreign language
This course is taught partially in Italian and partially in a foreign language. Study materials can be provided in the foreign language and the final exam can be taken in the foreign language.
Assigned to the Degree Course
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The course is focused on the acquisition of the fundamental principles of medical genetics, genetic diseases, and personalized genomic medicine.
The course will provide students with the knowledge of the mechanisms of genetics in medicine. The course aims to share knowledge on genetic diseases, their mechanisms and therapeutic perspectives. Particular attention is paid to the principles of personalized genomic medicine and to the applicative possibilities of pharmacogenomics in clinical practice.
-> First part
The human genome, genes, and chromosomes
Chromatin, heterochromatin, dose compensation, chromosomes in mitosis and meiosis. Genes structure and the human genome.
Gametogenesis and zygote
Zygote generation, chromosomal determination of sex
Human karyotype, mitotic chromosomes, banding techniques, meiotic chromosomes
Mutations, number and structure abnormalities, sex chromosomes, X chromosome inactivation, X female abnormalities, sex chromosome abnormalities in males
Study of family trees
Monogenic disorders, autosomal dominant inheritance, recessive and sex-related
Exceptions to Mendelian inheritance
Issues related to the interpretation of family trees. Variable expressivity and incomplete penetrance (Ex: Holoprosencephaly). Genetic heterogeneity (Ex: deafness). Late-onset diseases and anticipation (Ex: Huntington's disease). Unbalanced X chromosome inactivation and X / autosomal translocations. Germinal and somatic mosaicism. Mitochondrial inheritance (examples of mitochondrial diseases). Imprinting.
Molecular epidemiology and susceptibility to multifactorial diseases
Polygenic diseases: Quantitative and semi-quantitative characters. Evaluation of the genetic component in complex genetic diseases. Strategies for the identification of susceptibility genes.
Mono-dizygotic twins, control of sexual development, genetic defects of embryonic development: Homeobox and Hedgehog genes, Defects in limb development.
Disorders of sexual development
Determination of gonadal sex and differentiation of phenotypic sex
Genetic testing and genetic counseling
Genetic counseling and diagnostic tests with different utilities and applications: prenatal, postnatal, screening, presymptomatic and susceptibility. The genetic report, diagnostic pathways
Chorionic villus sampling. Amniocentesis. Cordocentesis. Cytogenetic analysis, Molecular analysis. Preimplantation, genetic diagnosis. Future developments: non-invasive prenatal diagnosis
PCR, Real-Time PCR, Sequencing
-> Second part
Genetically determined Human diseases. The following will be treated: Biological and genetic bases of diseases. Placement within diagnostic pathways. Gene therapy. Practical and interpretative exercises, risk calculation, drafting of a genetic report.
Introduction to genomics and post-genomics.
IT services and tools in genetic diseases. Database of pathologies and variants. Interpretation of variants based on computer databases and scientific literature. Identification of disease genes: Functional cloning and positional cloning, the candidate-by-position gene approach. The Human Genome Project and the use of the human genome sequence for the identification of disease genes. New generation sequencing and its clinical applications. International databases
Chromosomal syndromes and genomic disorders
Main chromosomal aberration syndromes: Trisomy 13, trisomy 18, trisomy 21. Cry-du-chat syndrome. Wolf syndrome. Turner and Klinefelter syndrome. CGH arrays and cryptic chromosomal rearrangements. Diagnostic approach to intellectual disability. Abnormalities of sex chromosomes
Diseases caused by genomic imprinting
Angelman syndrome. Prader-Willi syndrome. Genomic imprinting and medically assisted procreation
The most common genetic disorders
Cystic fibrosis and pathologies related to the CFTR gene, Thalassemia and Hemoglobinopathies, Hemochromatosis,
Diseases caused by dynamic mutations
Fragile X chromosome syndrome. Myotonic dystrophy. Huntington's disease. Kennedy's disease. Friedreich's ataxia. Autosomal dominant spinocerebellar ataxia.
Neurological and neurodegenerative disorders and complex phenotypes
Movement disorders: Spastic paraplegies, Parkinsonisms, Ataxias, Dystonia. Genetically-determined dementias: Alzheimer's, frontotemporal dementias. Neuromuscular diseases: Spinal muscular atrophy, Amyotrophic lateral sclerosis (ALS), Muscular dystrophy, Hereditary peripheral neuropathies
Hereditary primary cardiomyopathies. Hypertrophic cardiomyopathy. Left ventricular non-compaction. Dilated cardiomyopathy. Arrhythmogenic cardiopathies
Retinitis Pigmentosa, Usher Syndrome, Stargar's Disease, Retinal Macular Degeneration
Orphan drugs and the complexity of the genetic component. Applications of the clinical exome.
Bioinformatics, Minigene assay, Generation IPS cells
Methods and clinical trials concerning the pathologies addressed. Outline of Gene Transfer, Targeting of transgenes, RNA interference, CRISPR and gene editing.
Main applications of gene therapy in hereditary diseases (Cystic fibrosis; Hereditary coagulopathies). Specific aspects of tumor gene therapy
Hereditary tumor syndromes, somatic mutations, oncogenes and tumor suppressors
The study of inter-individual variability, Molecular typing, Interpretation of profiles, biostatistic calculation
Involvement of the microbiome in the pathophysiology of human disease
-> Third part
Pharmacogenetics, pharmacogenomics. Pharmaco-epigenetics. Sequencing of the human genome and interindividual variability.
Interindividual variability in efficacy and tolerability in response to drug therapy
Enzymes responsible for drug metabolism, genes coding for the drug's therapeutic target, genes that influence drug response: pharmacokinetics (proteins involved in the bioavailability of the drug), pharmacodynamics (genes that code for the drug's therapeutic target)
Pharmacogenetics in clinical practice
Molecular tests, development of new drugs. Cytochrome genes, KRAS / NRAS, BRCA1 / 2
Pharmacogenomics and study technologies
Identification of molecular targets and biomarkers. Sequencing of tumor genomes
Use of liquid biopsy in clinical practice. Diagnostic, prognostic and predictive value in cancer pathologies
The drugs that need a genetic test for their administration
Learning Achievements (Dublin Descriptors)
D1 - Knowledge and ability to understand. The student will show mastery in basic knowledge of molecular genetics, cytogenetics, familial pedigrees, patterns of disease transmission, pharmacogenomics and personalized medicine.
D2 - Ability to apply knowledge and understanding. The student will demonstrate understanding of concepts and theories provided by the course; students will provide examples of genetic diseases (biological, clinical, hereditary, and analytical skills); they will be able to analyze familial pedigrees, identifying patterns of transmission, recurrence risks, available tests.
D3 - Autonomy of judgment.The student will show the ability to use knowledge and concepts that allow to apply logic of the discipline. In particular, students have to be able to identify appropriate personalized medicine strategies in order to administer pharmacogenetic tests; they will simulate the design of diagnostic pathways; they will be able to propose possible solutions to problematic cases.
D4 - Communication skills. The student will show the ability to communicate the knowledge acquired to their colleagues and superiors using appropriate terminology.
D5 - Learning skills. The student will show possession of the learning ability useful for the continuous updating of knowledge in this discipline.
The teaching material prepared by the lecturer in addition to recommended textbooks (such as for instance slides, lecture notes, exercises, bibliography) and communications from the lecturer specific to the course can be found inside the Moodle platform › blended.uniurb.it
Exercises in e-learning mode
Didactics, Attendance, Course Books and Assessment
The course includes frontal lessons, exercises, and research programmes
- Course books
Tom Strachan, Judith Goodship, Patrick Chinnery. "Genetica e Genomica". Zanichelli editore
Tom Strachan, Andrew Read. "Genetica molecolare Umana" Zanichelli editore
James Swarbrick. "Pharmacogenomics"
Dale Halsey Lea, Dennis J. Cheek, Daniel Brazeau, Gayle Brazeau. "Mastering Pharmacogenomics: A Nurse’s Handbook for Success"
Nadine Cohen. "Pharmacogenomics and Personalized Medicine"
Oral exam. To attend the final exam, students have to complete all the planned exercises in e-learning mode
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