GENETICA MEDICA, TECNICHE DI CITOGENETICA E METODICHE DIAGNOSTICHE DI PATOLOGIA CLINICA

Learning Objectives

• Medical Genetics

  At the end of the 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 molecular basis of developmental and cancer genetics. Know the basic principles of Genetic counselling.

• Cytogenetics

  At the end of the course the student should be able to:

  -understand the structure of the human genome and know the main mechanisms that may disrupt its architecture. To know the main techniques in the field of the classical and molecular cytogenetics, and the use of NGS techniques in order to identify the structural anomalies of the genome both in pre and postnatal settings.

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  The objective of the Course is to enable the student to acquire the basic notions for the critical evaluation and interpretation of the results of the main laboratory diagnostic techniques.

Course Structure

• Medical Genetics

  frontal teaching.

  Should teaching be carried out in mixed mode or remotely, it may be necessary to introduce changes with respect to previous statements, in line with the programme planned and outlined in the syllabus

• Cytogenetics

  Frontal teaching.

  Should teaching be carried out in mixed mode or remotely, it may be necessary to introduce changes with respect to previous statements, in line with the programme planned and outlined in the syllabus.

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  Polyclonal and monoclonal antibodies. Production techniques: Hybridomas and Phage Display

  ELISA techniques

  ELISPOT

  Flow cytometric techniques

  Western Blot

  Immunofluorescence

  Principles of Microarray and Sequencing

  Examples of clinical applications of laboratory techniques

Detailed Course Content

• Medical Genetics
  1. 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

  2. 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

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

  4. Population Genetics
     1. the Hardy-Weinberg equilibrium and its deviations
     2. Founder effect and genetic drift

  5. 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 human genome : The copy number variants
        3. Mechanisms of of copy number variants formation
     3. Uniparental disomy
        1. Trisomic e monosomic rescue
     4. Technical approaches for chromosome structure analysis
        1. Karyotype
        2. FISH
        3. Array-CGH and SNP-array

  6. Developmental Genetics
     1. Abnormalities of the signaling pathways: FGF, SSH, Wnt e TGF-β
     2. Transcription factors

  7. Cancer genetics
     1. Tumor Suppressor genes
     2. Oncogenes
     3. Hereditary cancer

   

  8. Genetic counselling
     1. Definition and principles
     2. Recurrence risk , the bayesian method

  9. New techniques in molecular genetics
     1. NGS
     2. NIPT
• Cytogenetics

  • The double helix structure

  • Chromosomes structure and their morphology

  • Classical Cytogenetics and banding techniques

  • The caryotype and its diagnostic indications

  • FISH analysis

  • Array-CGH and pathogenic mechanisms of the CNVs

  • Statistical analysis of array signals

  • SNP-array

  • Validation methods of genomic imbalances (MLPA, RealTime-PCR)

  • The next generation sequencing approach

  • The use of whole genome sequencing for the identification of genomic structural variants

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  Polyclonal and monoclonal antibodies. Production techniques: Hybridomas and Phage Display

  ELISA techniques

  ELISPOT

  Flow cytometric techniques: basics; compensation; cell cycle study; analysis of apoptosis

  Electrophoresis, isoelectric focusing, Western Blot, Western blot 2D

  Immunofluorescence

  Microarray patforms; normalization and preprocessing of raw data; first and next generation Sequencing;

  Examples of clinical applications of laboratory techniques: serum proteins electrophoresis; autoantibodies

Textbook Information

• Medical Genetics

  Genetica Umana e Medica (Neri, Genuardi), seconda edizione, Elsevier

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

• Cytogenetics

  1.Testo Atlante di Citogenetica Umana (Ventruto, Sacco, Lonardo)

  2. Computational exome e genome analysis CRC press 2018

  3. Teacher's documentation

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  Mauro Maccarrone. Metodologie Biochimiche e Biomolecolari. Zanichelli. 2019