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 to provide an in-depth understanding of the multiple inheritance patterns of genetic diseases and their underlying molecular causes. In addition, we will present the variety of experimental approaches to the study of human genetic diseases, including cytogenetic techniques and new DNA sequencing technologies. We will also address aspects of bioinformatics related to DNA sequencing and approaches to investigate the functional impact of variants. We will then address the basic concepts of tumor genetics and population genetics. Finally, the course will provide information on the inheritance of common polygenic and multifactorial disorders and present methods for identifying genetic 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.
The practical Laboratory session will be held at the laboratories of the Unit of Medical Genetics at Gaslini Institute (Genova).
Any Student with documented Specific Learning Disorders (SLD), or with any special needs, should contact the Lecturer(s) and to the dedicated SLD Representative in the Department before class begins, in order to liaise and arrange the specific teaching methods so that the learning aims and outcomes may be met.
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
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
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 (Overview)
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)
Interpreting the functional role of mutations by cellular approaches
Silencing
Overexpression
Gene editing
Precision medicine in genetics
Pharmacological targeting of mutations in Cystic Fibrosis
Hardy-Weinberg Equilibrium
Factors influencing H.W. equilibrium Mutation
Genetic drift
Migration
Non-random mating
Natural selection
Neutral Theory
Complex inheritance
Variance and Heritability
Concordance in twins, relative risk ratio, empiric risks
Discontinuous and Continuous traits
Mapping of complex traits
Linkage disequilibrium
Association studies
Sequencing studies and Gene Burden test.
Definitions and classifications
Principles of cancer genetics
Oncogenes and tumor suppressor genes
Mechanisms underlying tumorigenesis
Hereditary Cancel syndromes
Bioinformatic pipelines for NGS data analysis
Spatial profiling of gene expression by RNA scope, single-cell RNAseq and cell imaging
Advanced cell models (iPS cells and neurons, 2D and 3D epithelial respiratory cell models
Functional tests (ion imaging, patch-clamp and MEA electrophysiology)
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:
Ricevimento: For appointment please write to: federico.zara@unige.it or telephone 010-56363816
Ricevimento: Please, make an appointment by e-mail paolo.scudieri@unige.it, or telephone 010-56362606.
CLAUDIA CANTONI (President)
FEDERICO ZARA (President)
RENATA BOCCIARDI
ALDAMARIA PULITI
PAOLO SCUDIERI
NICOLA TRAVERSO
CHIARA VITALE
II semester, March.
The timetable for this course is available here: EasyAcademy
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.
