Medical genetics, Cytogenetics Techniques and diagnostic methodology

Module 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.

Objectives according to the Dublin Descriptors

1) Knowledge and understanding

At the end of the course, the student knows and understands the fundamentals of medical genetics: the main types of genetic and genomic variation and their phenotypic consequences; Mendelian inheritance patterns and the main non-Mendelian mechanisms (reduced penetrance/variable expressivity, mosaicism, imprinting, uniparental disomy, trinucleotide repeat expansions, mitochondrial inheritance); basic concepts of population genetics applied to risk assessment; chromosomal bases of genetic diseases and core principles of the main diagnostic methods (karyotype, FISH, array, NGS).

2) Applying knowledge and understanding

The student is able to apply the acquired knowledge to: analyse pedigrees and identify the most likely mode of inheritance; perform basic genetic risk estimates in standard scenarios, including elementary notions of allele frequency and an introductory Bayesian approach; recognise conditions in which non-Mendelian mechanisms may play a role; orient themselves in selecting the most appropriate genetic test among those covered, understanding its aims and general limitations.

3) Making judgements

The student develops basic independent judgement in interpreting essential clinical-family and genetic information; can discuss simple alternative hypotheses (e.g., monogenic vs chromosomal causes; Mendelian vs non-Mendelian inheritance) and evaluates, at an introductory level, the appropriateness and limitations of the main genetic tests in relation to the clinical question.

4) Communication skills

The student is able to communicate clearly and using appropriate terminology the core concepts of medical genetics; correctly describes inheritance patterns, expected outcomes of genetic tests and basic risk estimates; presents course topics orally in a coherent and structured way, connecting different areas of the syllabus.

5) Learning skills

The student has independent learning skills to consolidate and deepen knowledge through textbooks and teaching materials; integrates basic concepts to address standard medical genetics questions; maintains an introductory level of updating on the clinical applications of molecular genetics technologies and massively parallel sequencing.

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

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. The utility of the next generation sequencing in genetic diagnosis

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

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