Module I: Human Genetics and Genomics
Knowledge and understanding (Knowledge and know)
Development of the conceptual tools necessary for a critical analysis of the current genetic paradigms in human genetics. After attending the course, students will acquire a comprehensive knowledge of the theoretical and practical tools needed for the critical evaluation of the most recent achievements in the fields of Human Molecular Genetics and Human Genomics (and its multiple applications).
Applying knowledge and understanding (Skills and know how)
Achievement of the ability to apply the acquired knowledge in relation to the professional approach. Achievement of the comprehension skills required to develop and maintain issues related to the acquired knowledge, by means of critical reasoning and problem-solving attitudes.
Basic molecular genetics background as well as biochemical, physiological and cellular/molecular biology basic notions are required.
MODULE OF GENOMICS (4 CFUs, 32 hours)
• From Genetics to Genomics: introduction to the theoretical issues and the main technological achievements leading to the birth of genomic science.
• Genome project, part 1: Rationale, aims and planning. Polymorphic genetic markers and genetic maps. Assembly of the first genomic maps for the human and animal models genomes. Theoretical basis of linkage analysis in humans. Calculation of LOD scores and recombination fraction in the human genome. Autozygosity mapping approaches.
• Genome project, part 2: Introduction to the physical maps of a genome. Somatic cell and radiation hybrids. Physical maps based on FISH assays. Genomic libraries and assembly of recombinant clone contigs by fingerprinting or STS-content mapping. Transcription maps of the genome. The EST project.
• Genome project, part 3: Theoretical issues concerning genome sequencing. Human genome sequencing: the “clone-by-clone” e “whole genome shotgun” approaches. The public and private human genome projects. Validation and implementation of the human genome sequence assembly.
• The post-genomic era: Genome annotation approaches. The informational content of the human genome. Gene number and biological complexity: toward a new definition of “gene”. The GeneOntology and EnCODE projects.
• Genome transplantation: an avenue for synthetic life.
• Functional Genomics: Forward and reverse genomics approaches in the most used model organisms.
• Genomic approaches for the genetic dissection of complex diseases: Linkage disequilibrium mapping. The advent of SNP markers and the HapMAp project. Genome-wide association studies (GWAS). Introduction to personal genomics. Approaches for next generation sequencing. The 1000 genome project. .Mapping human disease genes by exome sequencing.
MODULE OF HUMAN GENETICS (4 CFUs, 48 hours)
• Burden of genetic diseases: type and frequency, geographical distribution, monogenic vs. polygenic and multifactorial, effect size vs. allele frequency.
• Inheritance of genetic diseases: monogenic diseases and their complexity, heterogeneity associated with genetic diseases, genetic heterogeneity, phenotypic heterogeneity, pleiotropy.
• Complexity of monogenic diseases: beyond Mendel and new paradigms in human genetic, multifactoriality of the phenotype (modifier genes, genetic background, epigenetic mechanism, stochastic event in morphogenesis, influences of the environment).
• Epigenetic processes: semantic connotations, concept of “Waddington epigenetic landscape” as representation of developmental processes. Examples: cell fate and developmental dynamics of cell differentiation.
• Flexibility of the genome: concept of genetic linear pathway, role of pleiotropy and redundancy, networks as better representations of gene interactions.
• Genotype-phenotype relationships: non linearity and role of stochasticity, the stochastic nature of gene expression, concept of incomplete penetrance (stochasticity in development), canalization, plasticity, norm of reactions, concept of phenotypic and genotypic space.
• Variation of phenotype: causes (genetic differences, environmental influences, stochastic developmental events), concept of developmental variation (intangible variation)
• Heritability: definition, broad and narrow heritability, phenotypic variance, the analysis of variance and analysis of causes, genetic, biological and statistical epistasis.
• Gene-environment interactions: concepts of additive and multiplicative models and their inadequacy as an explanation of gene-environment interactions. Phenylketonuria as an example of gene-environment interactions.
• Introduction to system dynamics: scale free networks and structural architecture of gene regulatory networks, concept of state space, attra
MODULE OF GENOMICS: The teaching material is updated regularly and will be provided to all students in the e-learning online platform as Powerpoint slides file, short notes, animation files and articles from scientific literature on selected issues.
• TA Brown – “Genomes 3” (Garland Science Publ.)
• T Strachan & A. Read – “Human Molecular Genetics” (Garland Science Publ.)
• J Watson, R Meyers, A Caudy & J Witkowski - “Recombinant DNA: genes and genomes” (W.H. Freeman & Co)
MODULE OF HUMAN GENETICS : Powerpoint slides and articles from scientific literature on specific topics will be provided.