03553 - Medical Genetics (B)

Learning outcomes

The course aims to provide both established and emerging knowledge in the field of Medical Genetics, while also emphasizing its cross-disciplinary relevance to all areas of medicine. By the end of the course, students will be able to:

• Draw pedigrees and understand inheritance patterns of genetic diseases
• Calculate the recurrence risk of Mendelian disorders
• Recognize atypical inheritance patterns
• Understand the principles underlying the development of multifactorial diseases
• Know how genetic testing is performed and interpret its results
• Be aware of genetic predispositions to cancer
• Understand the fundamentals of clinical genetics and genetic counseling

Course contents

Genetic Causes of Diseases: Types of Variants and Their Clinical Impact

Monogenic Disorders: Definition; construction and analysis of pedigrees
Risk Calculation: Estimating the recurrence risk of genetic diseases
Exceptions to Mendelian Inheritance: Variable expressivity, incomplete penetrance, genetic heterogeneity, late-onset disorders, anticipation
Mosaicism: Germline and somatic mosaicism
X-Chromosome Inactivation: Skewed X-inactivation and X/autosome translocations
Mitochondrial Inheritance: Examples of mitochondrial diseases; differences between nuclear and mitochondrial DNA

Gene Identification

• Historical approaches (e.g., linkage analysis)
• Modern approaches

Population Genetics

• Hardy-Weinberg equilibrium and carrier frequency
• Bayes’ Theorem

Chromosomal Disorders

• Numerical abnormalities
• Structural abnormalities (translocations, ring chromosomes, marker chromosomes)
• Contiguous gene syndromes (microdeletions, microduplications)
• Genomic imprinting disorders and uniparental disomy (examples of imprinting-related conditions)

Multifactorial Conditions

• Multifactorial inheritance
• Genetic predisposition and threshold models
• Population-based studies: association studies, GWAS, linkage disequilibrium, common disease–common variant hypothesis
• Polygenic Risk Scores (PRS) and their clinical application

Cancer Genetics

• Hereditary cancer predisposition syndromes

Clinical Genetics

Genetic Counseling: Indications, goals, and types

• Pedigree reconstruction
• Recurrence risk calculation in Mendelian disorders
• Choosing the diagnostic approach (direct and indirect diagnosis, preimplantation diagnosis, prenatal diagnosis, etc.)
• Clinical interpretation of genetic test results
• Cascade genetic testing

To ensure students fully understand how to apply theoretical knowledge of Medical Genetics in clinical practice, a variety of real clinical cases will be presented and discussed. These cases will be proposed both by the instructor and by the students, with in-depth analysis of the test results and their specific clinical implications.

Readings/Bibliography

GENETICA UMANA E MEDICA - V EDIZIONE

Edra Edizioni

Authors: Neri G., Genuardi M.

Published: 01/01/2024

Language: italian

Online teaching modules in English: https://www.primarycaregenetics.org/?page_id=109&lang=en

Online teaching modules in Italian: https://www.primarycaregenetics.org/?page_id=900&lang=it

Teaching methods

Formal lessons, exercises, interactive clinical cases discussion

Assessment methods

During the oral test, the student will be asked to comment the outcome of molecular analyses or a clinical case randomly selected from a pool, by using the information and the competences acquired during the course, including drawing the family pedigree according to the information provided, and calculating recurrence risks.

Attention will be paid to the use of proper technical language and to the ability to explain the concepts clearly even for any future patients.

The mark obtained in the Medical Genetics test concurs to the final mark for the integrated course according to the proportion of credits. The final mark is discussed and decided by the whole commission at the end of the test day.

Teaching tools

In the course's virtual space, the students will find:

- The slides presented during the lessons and additional material (papers or video focussing on specific topics)

- Exercises and solutions with explanations

- Links to useful websites

- A Forum to share questions and answers

Office hours

See the website of Alessandro Vaisfeld