BIOLOGIA, GENOMICA, GENETICA UMANA E MEDICA

10 CFU - 1° Semester

Teaching Staff

MICHELE PURRELLO - Module BIOLOGY, GENOMICS, HUMAN GENETICS - BIO/13 - 6 CFU
CINZIA SANTA DI PIETRO - Module BIOLOGY, GENOMICS, HUMAN GENETICS
FULVIA SINATRA - Module BIOLOGY, GENOMICS, HUMAN GENETICS
MARCO FICHERA - Module Medical Genetics - MED/03 - 4 CFU
TERESA MATTINA - Module Medical Genetics

Learning Objectives

BIOLOGY, GENOMICS, HUMAN GENETICS
To obtain advanced knowledge and competences in Human Biology, Genetics and Genomics, related to Biotechnology and its translational applications to Medicine
Medical Genetics
At the end of course, students should be able to:

Describe the types of genetic variation seen in the human genome and explain how these variations affect disease states and diversity of normal variation. Perform pedigree analysis and apply principles of inheritance in calculating genetic risk for a variety of genetic disorders and patterns of inheritance; and incorporate knowledge of population genetics to calculate genetic risk based on carrier frequency within a population. Explain and identify non-Mendelian mechanisms such as: reduced penetrance, variable expressivity, uniparental disomy, mosaicism, genomic imprinting and unstable repeat expansion. Understand the basic principles of Genetic counselling. The student should also be able to understand the technical basis of the principal genomic tests such as array-CGH/SNP and NGS, to evaluate their clinical and analytical sensitivity and specificity, and their predictive values.

Course Structure

BIOLOGY, GENOMICS, HUMAN GENETICS
Lectures through powerpoint presentations
Medical Genetics
Frontal teaching and practical exercises

Detailed Course Content

BIOLOGY, GENOMICS, HUMAN GENETICS
The Human Genome Project (HGP) and the genome projects of a plethora of other organisms and viruses have profoundly modified our knowledge on their biology and accordingly the perspectives of its translational applications to Biotechnology and BioMedicine. Progress in the fields of: Molecular Medicine [Genomics (including ncRNAs), Epigenomics, Transcriptomics, Proteomics (including protein post-translational modifications), Interactomics, Human Pathogenomics], Computational Biology, Bioinformatics, Biotechnology have determined an important evolution of Human Biology, Genetics and Genomics. This academic discipline aims to allow students to gather a global vision of the structure of organisms and their cells, together with their physiological functions and alterations in pathology: the final aim is the design of rational biotechnological manipulations. The Course on Human Biology, Genetics, Genomics comprises advanced seminars on the biomolecular structure of our genome and organism [eg, the biomolecular functions of non coding RNAs (ncRNAs), their biological roles, and involvement in pathology; microvesicles, exosomes, their molecular cargo and corresponding biomolecular functions]: it aims to transmit to the students an unifying vision of Human Biology, Genetics and Genomics and to allow them to insert this knowledge in the context of our organism and of human Physiopathology. The ensuing comprehension of the human biological logic should allow students to understand the conceptual bases of Biomolecular Medicine and their medical biotechnological applications. The course, which features a peculiar Top > Down approach, comprises a series of advanced seminars on Molecular, Genome and Complex Systems BioMedicine. Specifically, it describes projects as Encode, The Human Methylome, The Human Proteome, The Human Interactome, which have determined a critically important evolution of our knwoledge of genome structure and functions. The omic structure of cellular machineries and apparati (Cell Cycle Machinery, DNA Replication Machinery, DNA Repair Machinery, Transcription Apparatus, Protein Synthesis Machinery, Machinery for the Synthesis and Targeting of Microvesicles and Exosomes, Signal Transduction Apparatus, Apoptotic Machinery) will be analyzed aiming to correlate it to their biomolecular functions, involvement in pathology, and potential biotechnological modifications. Evolution is a constant theme throughout the course. Students are invited to undergo an intense laboratory training to acquire appropriate working knowledge on Molecular Medicine and Biotechnology. The Section of Biology and Genetics of the Department of Biomedical Sciences and Biotechnology has the instrumentation needed to perform advanced research in Molecular Medicine and Biotechnology.

Course Plan
-Genome BioMedicine: Definition, History, fields of investigation, prospective contribution to
Medicine.
-Molecular and Complex Systems BioMedicine: the Olystic Approach to the study of organisms
and their cells - From the Omics to the biology of organisms and their cells.
-Genome Projects and the Gene Candidate Approach to study the phenotype and the functions
of genes.
-Gene and genome expression regulation.
-Advanced High Throughput technologies (Including Biotechnologies) to study cell structure and
functions.
-Polymerase Chain Reaction (PCR) and its experimental applications.
- Experimental technologies for Genome and Transcriptome modification (eg, CRISPR).
-Computational Biology and BioInformatics.
-Cell Machineries and Apparati: genome structure, molecular structure, evolution, related
pathology (eg, Cell Cycle and DNA Duplication Machinery, Transcription Machinery, Apparatus
For Synthesis of Microvesicles and Exosomes and Cargo Loading, Signal Transduction
Machinery, Apoptotic Machinery).
-A new vision of the Genome: critical biomolecular roles of non coding RNAs (ncRNAs) in gene
regulation and their involvement in genetic pathology.
-The Encode Project.
-The Human Proteome Project.
-The Human Methylome Project.
-The Human Interactome Project.
-Biological networks: structural and functional complexity, analytical methods, experimental
applications.
-Stem Cells: biology, biotechnology, therapeutic applications.
-Biodiritto e Bioetica: legislazione, filosofia morale.

Medical Genetics

Genetic and genomic variations and their causes
1. Concepts of polymorphism and mutation and their evolutionary significance
2. Functional Classification of sequence mutations
3. Costitutional and somatic mutations
4. Hardy-Weinberg equilibrium and deviations
5. Founder effect and genetic drift
6. Polymorphic Markers, haplotypes and linkage analysis
7. Principal sources of genetic and genomic variations
8. DNA repair mechanisms
9. Functional classification of mutations

Inheritance patterns of Mendelian and sex-linked genetic diseases
1. Dominant, recessive and sex-linked alleles
2. Pseusodominant and digenic inheritance
3. Penetrance and expressivity
4. Mosaicism
5. Genomic imprinting
6. Anticipation and repeat expansion diseases

Other patterns of inheritance
1. Mitochondrial inheritance
2. Polygenic and multifactorial inheritance
3. Models of multifactorial diseases
4. The genetic basis of complex diseases

The chromosomal basis of genetic diseases
1. Abnormalities of chromosome number and meiotic non-disjunction
  1. Turner syndrome , Down syndrome , Edwards syndrome, Patau syndrome
2. Abnormalities of chromosomal structure
  1. Translocations, Inversions, deletions, duplications
  2. The plasticity of the human genome : The copy number variants
  3. Mechanisms of copy number variants formation
3. Uniparental disomy
  1. Trisomic and monosomic rescue
4. Technical approaches for chromosome structure analysis
  1. Karyotype
  2. FISH
  3. Array-CGH and SNP-array

Genetic Tests
1. Sensitivity and specificity of diagnostic tests.
2. Baysian probability and predictive values.
3. Array-CGH e SNP-array
  1. Statistical analysis of signal and CNV calling
  2. The utility of the CNV databases
4. Next generation sequencing (NGS)
  1. Methods and indicators
  2. Base calling
    1. Phred score, coverage e binomial distribution of the reads
  3. Genotype calling algorythms
    1. Fixed thresholds and bayesian methods
  4. Gene Panel, WES e WGS
  5. Diagnostic workflow and previsional softwares
  6. Diagnostic Indicators
  7. Reports and incidental findings

Genetic counselling
1. Definition and principles
2. Recurrence risk

Textbook Information

BIOLOGY, GENOMICS, HUMAN GENETICS
Molecular and Cellular Biology, Lodish et Al.
Molecular Biology of the Cell, Alberts et Al.
Genetics in Medicine, Thompson e Thompson.
Human Molecular Genetics, Strachan et Al.
Medical Genetics
Genetica Umana e Medica (Neri, Genuardi), seconda edizione, Elsevier

Medical Genetics (Jorde, Carey, Bamshad) fifth edition, Elsevier

Open in PDF format Versione in italiano