HUMAN GENETICS AND LABORATORY

iten
Code
95306
ACADEMIC YEAR
2021/2022
CREDITS
5 credits during the 1st year of 10598 MEDICAL-PHARMACEUTICAL BIOTECHNOLOGY (LM-9) GENOVA
SCIENTIFIC DISCIPLINARY SECTOR
MED/03
LANGUAGE
English
TEACHING LOCATION
GENOVA (MEDICAL-PHARMACEUTICAL BIOTECHNOLOGY)
semester
2° Semester
Teaching materials

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

Office hours: For appointment please write to: federico.zara@unige.it or telephone 010-56363816

Office hours: Please, make an appointment by e-mail paolo.scudieri@unige.it, or telephone 010-56362606.

Exam Board

FEDERICO ZARA (President)

CLAUDIA CANTONI (President)

RENATA BOCCIARDI

ALDAMARIA PULITI

PAOLO SCUDIERI

NICOLA TRAVERSO

CHIARA VITALE

LESSONS

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.

 

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