GENETICA MEDICA III ANNO

MED/03 - 6 CFU - 1° Semester

Teaching Staff

MARCO FICHERA


Learning Objectives

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

Frontal teaching and practical exercises.

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.



Detailed Course Content

  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
    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

  1. 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

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

  1. 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

  1. 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

  1. Genetic counselling
    1. Definition and principles
    2. Recurrence risk

 



Textbook Information

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

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




Open in PDF format Versione in italiano