03553 - Medical Genetics

Learning outcomes

Learning the recent innovations obtained in recent years in the field of Medical Genetics and offer the tools to be able to transfer these acquisitions to clinical practice. At the end of the course, the student is able to reconstruct family trees, interpret the segregation of hereditary diseases, and calculate the risk of recurrence of the same; to knows linkage analysis and reconstruct haplotypes; he will also knows the exceptions to Mendelian-type inheritance, the principles underlying complex genetic diseases, and the methods of diagnosing a genetic disease; he will learned the purposes and methods of carrying out genetic counseling also from a gender perspective.

Course contents

Genetic disorders

• classes of genetic disorders
• genetic counselling: indications, purpose, pedigree reconstruction
• genetic testing: indications, purpose, methodologies (review)
• genetic variation and terminology (review)
• online resources

Mendelian inheritance and risk assessment

• Mendelian inheritance patterns
• Hardy-Weinberg principle and carrier frequency
• Bayes theorem
• Calculation of risk of recurrence in recessive pedigrees

Irregularities of mendelian inheritance

• de novo mutations and mosaicism
• incomplete penetrance
• variable expressivity
• anticipation in triplet repeat disorders
• genetic heterogeneity - locus and allelic
• clinical heterogeneity and allelic disorders
• pseudoautosomal inheritance of X-linked traits
• male lethality in X-linked pedigrees
• skewed X-inactivation
• oligogenic inheritance

Mendelian disorders

• Spinal Muscle Atrophy
• Huntington disease
• Cystic fibrosis
• Duchenne and Becker muscular dystrophies

Genomic imprinting and UPD

• Prader-Willi syndrome and Angelman syndrome

Mitochondrial inheritance

• mitochondrial DNA
• maternal inheritance pattern
• irregularities of maternal inheritance: heteroplasmy/homoplasmy, mitochondrial threshold effect, mitochondrial bottleneck
• mitochondrial disorders

Disorders of genomic imprinting and UPD

• Prader-Willi Syndrome, Angelman Syndrome

Multifactorial disorders

• multifactorial inheritance
• genetic susceptibility and liability threshold model
• family studies: familial aggregation, twin concordance, adoption studies
• population studies: association, GWAS, linkage disequilibrium, common disease-common variant hypothesis

Onccogenetics: inherited syndrome with cancer susceptibility

Therapies

Gene Therapy and RNA drugs application in mendelian disorders

Preventive and therapeutic options in mitochondrial disorders

Readings/Bibliography

• Thompson and Thompson Genetics in Medicine, 8th Edition (2015). Robert L. Nussbaum, Roderick R. McInnes, and Huntington F. Willard. Elsevier.
• Medical Genetics, 6th Edition (2019). Lynn B. Jorde, John C. Carey, Michael J. Bamshad. Elsevier.
• Emery's Elements of Medical Genetics and Genomics 16th Edition (2021). Peter D Turnpenny, Sian Ellard, Ruth Cleaver. Elsevier.
• Articles/reviews on selected topics provided by the professor.

Teaching methods

Teaching/learning methods include:

• lectures supported by PowerPoint presentations
• problem-based learning: human genetics problems to be solved in class with active student participation
• case report discussion: student are allowed to bring clinical history/case of their interests. 

Assessment methods

Students' knowledge and understanding of medical genetics will be assessesed and graded as a component of the Integrated Course (I.C.) in Pediatrics.

Learning assessment will be carried out in two steps and graded on a 30 point scale:

· 1) Written assessment: each student is asked to write a synopsis of a genetic disorder chosen from a list that will be provided; the synopsis must be submitted 10 days prior to the exam session published in AlmaEsami for Pediatrics (I.C.). Detailed instructions will be provided in class. The written assessment will contribute 50% of the Medical Genetics grade.

· 2) Oral exam: the student will be asked to discuss the content of the written synopsis and/or answer relevant questions on the chosen disorder in order to demonstrate understanding of the topic. In addition, the student will be asked to resolve a medical genetics problem (e.g. interpret a pedigree or other clinical scenario, assess the risk of recurrence, caculate carrier frequency). The oral exam will contribute 50% of the medical genetics grade.

· The oral exam will be held on the date of the Pediatrics I.C. exam session published in AlmaEsami. Students must first submit the synopsis in order to take the oral assessment.

· The final grade awarded for the intergrated course will be based on the student's achievement in all learning activities that make up the integrated course. Honors (Lode) may be assigned for outstanding achievement, at the discretion of the examining commission.

Teaching tools

The following material will be available online through Virtuale:

• pdf files of all lectures
• selected articles/reviews on relevant topics

Office hours

See the website of Caterina Garone