Salta al contenuto principale della pagina

HUMAN GENETICS AND LABORATORY

CODE 95306
ACADEMIC YEAR 2021/2022
CREDITS
  • 5 cfu during the 1st year of 10598 MEDICAL-PHARMACEUTICAL BIOTECHNOLOGY(LM-9) - GENOVA
  • SCIENTIFIC DISCIPLINARY SECTOR MED/03
    LANGUAGE English
    TEACHING LOCATION
  • GENOVA
  • SEMESTER 2° Semester
    MODULES This unit is a module of:
    TEACHING MATERIALS AULAWEB

    AIMS AND CONTENT

    LEARNING OUTCOMES

    Knowledge of the mode of inheritance of genetic disorders in humans and the underlying molecular mechanisms. Comprehension of experimental approaches for the detection of genetic factors associated to human diseases. Basic concepts on population genetics.

    AIMS AND LEARNING OUTCOMES

    The course aims at deepening into the many pattern of inheritance of genetic disorders and the underlying molecular causes. In addition, we will present the variety of experimental approaches to the study of human genetic disorders, including cytogenetic techniques and novel sequencing technologies.  We will also deal with the management of bioinformatic data related to sequencing analysis. We will hence approach basic concepts of population genetics and factors influencing the distribution of variants. Finally, the course will provide information about inheritance of common polygenic and multifactorial disorders and presents methods to identify susceptibility factors.

    TEACHING METHODS

    The course is organized in frontal lessons held in English. The topics included in the syllabus will be explained by the professor through PowerPoint presentation, also using examples from scientific papers. Students will be stimulated to ask questions and formulate answers using interactive modalities.

     

    SYLLABUS/CONTENT

    MENDELIAN INHERITANCE AND GENETIC DISORDERS

    Inheritance in Men: A brief History

    Monogenic Disorders with Mendelian inheritance

    Autosomal dominant disorders                                                                              

    Autosomal recessive disorders                                                                               

    Other Monogenic Disorders     

    Chromosome X inactivation and X-linked disorders                                                        

    Y-linked disorders                                                                                                                        

    Mitochondrial inheritance                                                                                                                                        

    Beyond Mendel. Complex monogenic disorders

    Genetic Heterogeneity                                                                                                                                              

    Allelic Heterogeneity                                                                                                                                                 

    Variable expressivity and Incomplete penetrance                                                                                         

    Lethal alleles                                                                                                                                                                  

    Sex-limited traits                                                                                                                                                          

    Dynamic mutations and disease anticipation                                                                                                    

    De novo mutations, gonadal and somatic mosaicisms                                                                   

    Imprinting disorders and parent-of-origin gene expression                                                                       

     

    MUTATIONS IN GENETIC DISORDERS

    Polymorphic variants

    Classification of Mutations                                                                                                                                     

    Chromosomal disorders and Cytogenetics

    Human Karyotype                                                                                                                                       

    Numerical and structural chromosomal abnormalities: classifications and mechanisms                

    Abnormalities of Sex chromosomes                                                                                                                     

    Copy number variants (CNVs)                                                                                                                                

    Point Mutations

    DNA level: base substitution and base deletion/insertion                                                                          

    Protein level: Coding mutations                                                                                                                             

                      Allelic heterogeneity in Cystic Fibrosis, as example                                                                        

                      Nonsense mediated mRNA decay                                                                                                         

    Protein level: Non-Coding mutations                                                                                                                  

                     Mutations affecting splicing                                                                                                                     

                     Intronic mutations affecting non-coding functional elements                                                   

    Functional level: Loss- or gain-of-function                                                                                                        

     

    IDENTIFYING MUTATIONS IN GENETIC DISORDERS

    Conventional Cytogenetics for detection of chromosomal abnormalities

    Karyotyping and chromosome banding                                                                                                              

    International System for human Cytogenetics Nomenclature (ISCN)                                                                      

    Cytogenetics in the clinical practice                                                                                                      

    Molecular Cytogenetics for detection of Copy Number Variants (CNVs)

    Fluorescence in sit hybridization (FISH)                                                                                                              

    Comparative Genomic Hybridization (CGH)                                                                                                                      

    DNA microarrays

                   CGH Arrays                                                                                                                                                    

                   SNP Arrays                                                                                                                                                     

                   DNA microarrays in the clinical practice

    Sequencing

    Sequencing methods                                                                                                                                                 

                   Maxam-Gilber                                                                                                                              

                   Sanger                                                                                                                                                             

                   Massive parallel Sequencing (NGS) – Short Reads                                                                         

                  Single Molecule Sequencing – Long Reads                                                                                         

    Analysis of Sequencing data                                                                                                                                    

    Genetic Databases and Genome Browsers                                                                                                       

    Applications of Sequencing methods in human genetics                                                              

    Genetic Testing                                                                                                                                             

                    NGS: Exome Sequencing and interpretation of variants in the clinical setting                   

                    NGS: Detection of Structural Variations (NIPT)                                                                              

                    Long Reads Sequencing (Repeats and GC regions, De Novo Assembly)                                

     

    POPULATION GENETICS

    Hardy-Weinberg Equilibrium                                                                                                                                 

    Factors influencing H.W. equilibrium                                                                                                                   

                    Mutation                                                                                                                                                       

                    Genetic drift                                                                                                                                                 

                    Migration                                                                                                                                                      

                    Non-random mating                                                                                                                                 

                   Natural selection                                                                                                                                                         

                   Neutral Theory                                                                                                                                                             

                   Linkage Disequilibrium                                                                                                                                              

     

    POLYGENIC AND MULTIFACTORIAL DISORDERS

    Complex inheritance

    Variance and Heritability                                                                                                                                           

    Concordance in twins, relative risk ratio, empiric risks                                                                                 

    Discontinuous and Continuous traits

    Mapping of complex traits

    Association studies                                                                                                                                                      

    Sequencing studies and Gene Burden test           

    RECOMMENDED READING/BIBLIOGRAPHY

    Lecture notes and reviews covering the whole course will be available for the students in Aulaweb. In addition, students will be provided with files containing genetic problems with solutions

    Recommended reference textbook:

    • Strachan & Read: Human Molecular Genetics. Bios Scientific Publisher

    TEACHERS AND EXAM BOARD

    Exam Board

    FEDERICO ZARA (President)

    CLAUDIA CANTONI (President)

    RENATA BOCCIARDI

    ALDAMARIA PULITI

    PAOLO SCUDIERI

    NICOLA TRAVERSO

    CHIARA VITALE

    LESSONS

    LESSONS START

    II semester, March 2022

    EXAMS

    EXAM DESCRIPTION

    The exam is carried out as oral test in English or in Italian, as preferred by the student. The final vote is expressed out of 30.

    ASSESSMENT METHODS

    The oral exam, in English or Italian, will allow to test students on most of the content of the course, by assessing their knowledge on human genetics, as well as the acquired ability to connect different topics and to eventually solve genetic problems.

    Proficiency in English language, if opted by the student, will not be evaluated, but it must be sufficient to show the student’s knowledge of the subjects, with an adequate level of expertise.

    Exam schedule

    Date Time Location Type Notes
    25/01/2022 14:30 GENOVA Orale
    18/02/2022 14:30 GENOVA Orale
    17/06/2022 14:30 GENOVA Orale
    01/07/2022 14:30 GENOVA Orale
    19/07/2022 14:30 GENOVA Orale
    09/09/2022 14:30 GENOVA Orale
    23/09/2022 14:30 GENOVA Orale