| CODE | 95306 |
|---|---|
| ACADEMIC YEAR | 2022/2023 |
| CREDITS |
|
| SCIENTIFIC DISCIPLINARY SECTOR | MED/03 |
| LANGUAGE | English |
| TEACHING LOCATION |
|
| SEMESTER | 2° Semester |
| MODULES | This unit is a module of: |
| TEACHING MATERIALS | AULAWEB |
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.
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.
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.
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
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:
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.
FEDERICO ZARA (President)
CLAUDIA CANTONI (President)
RENATA BOCCIARDI
ALDAMARIA PULITI
PAOLO SCUDIERI
NICOLA TRAVERSO
CHIARA VITALE
II semester, March 2022
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.
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.
| Date | Time | Location | Type | Notes |
|---|---|---|---|---|
| 24/01/2023 | 14:30 | GENOVA | Orale | |
| 17/02/2023 | 14:30 | GENOVA | Orale | |
| 20/06/2023 | 14:30 | GENOVA | Orale | |
| 04/07/2023 | 14:30 | GENOVA | Orale | |
| 21/07/2023 | 14:30 | GENOVA | Orale | |
| 11/09/2023 | 14:30 | GENOVA | Orale | |
| 26/09/2023 | 14:30 | GENOVA | Orale |