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

MODULE 1

Genetic diseases

- Classification

- Genetic testing: indications, purposes, methodologies (review)

- Genetic and genomic variants, nomenclature (review)

- Online resources

Mendelian inheritance

- Models of Mendelian inheritance

- Irregularities in 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 models

- X inactivation

- Oligogenic inheritance

Mendelian disorders

- Spinal muscular atrophy

- Huntington's disease

- Cystic fibrosis

- Duchenne and Becker muscular dystrophies

Mitochondrial inheritance

- Mitochondrial DNA

- Maternal inheritance pattern

- Irregularities in maternal inheritance: heteroplasmy/homoplasmy, mitochondrial threshold effect, mitochondrial bottleneck

- Mitochondrial diseases

Newborn screening and therapies

- Newborn screening

- Gene therapy and application of RNA drugs in Mendelian diseases

- Preventive and therapeutic options in mitochondrial diseases

 

MODULE 2

Identification of disease genes

-Historical approaches (linkage analysis)

- Modern approaches

Population genetics

- Hardy-Weinberg principle and carrier frequency

- Bayes' theorem

Chromosomal disorders

Chromosomal number abnormalities

Chromosomal structural abnormalities (translocations, ring chromosomes, markers)

Contiguous gene syndromes (microdeletions, microduplications)

Genomic imprinting disorders and UPD

- Prader-Willi syndrome, Angelman syndrome

Multifactorial conditions

- Multifactorial inheritance

- Genetic predisposition and threshold models

- Population studies: association, GWAS, linkage disequilibrium, common disease-common variant hypothesis

- Polygenic risk scores (PRS) and their clinical use

Oncological genetics: Hereditary cancer predisposition syndromes.

Clinical genetics

Genetic counselling: Indications, purposes, types

- Reconstruction of the family tree

- Calculation of the risk of recurrence of Mendelian diseases

- Choice of diagnostic approach (direct and indirect diagnosis, pre-implantation diagnosis, prenatal diagnosis, etc.)

- Clinical interpretation of genetic test results

- “Cascade” genetic testing

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 assessed and graded as part of the Integrated Course (IC) in Paediatrics.

Learning assessment will be carried out in two stages and graded on a scale of 30 points:

1) Practical test Module 1 and Practical test Module 2: At the end of each module, students will take a virtual practical test, the score of which will contribute to the final exam grade. The practical test procedures will be detailed at the beginning of each module.

2) Oral exam: students will be asked to answer relevant questions regarding the practical tests and/or answer questions on Medical genetics topics. The oral exam will contribute 50% to the medical genetics grade.

- The oral exam will be held on the date of the Paediatrics I.C. exam session published on AlmaEsami.

- The final grade for the integrated course will be based on the results obtained by the student in all the teaching activities that make up the integrated course. At the discretion of the exam committee, honours (Lode) may be awarded in the case of excellent results.

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