71342 - Medical Genetics 1

Learning outcomes

At the end of the Medical Genetics 1 course, the student will: understand the molecular alterations underlying genetic diseases; be able to identify pathogenic variants according to international guidelines, by studying familial segregation and using omics databases; understand the strategies for identifying disease genes, including the use of new sequencing technologies.

Course contents

Introduction to medical genetics.

Monogenic diseases. Autosomal dominant inheritance, expressivity and penetrance, de novo mutations, germline mosaicism. Autosomal recessive inheritance. Sex-linked inheritance. X-chromosome inactivation. Non-Mendelian inheritance. Mitochondrial inheritance, maternal inheritance, heteroplasmy, threshold effect, random segregation, clinical manifestations. Dynamic mutations.

From the definitions of mutation and polymorphism to the concept of variant. ACMG criteria for the classification of genetic variants. Nomenclature of the main DNA, RNA and protein variants. DNA polymorphisms as genetic markers. Structural variants and methods for their identification, including array-CGH and SNP arrays.

The human reference genome. Databases. Genome sequencing projects in model organisms and their usefulness in medical genetics. Use of model organisms to study genetic diseases.

Sequencing technologies. Sanger sequencing, reaction setup and interpretation of electropherograms. Next-generation sequencing, including second- and third-generation sequencing, steps for the preparation of a sequencing reaction and analysis. Sequencing strategies, including multigene panels, mendeliome, whole-exome sequencing and whole-genome sequencing. Transcriptome analysis and use of disease-specific methylation profiles for diagnostic purposes.

Identification of disease genes. From functional cloning to positional cloning. Mapping of genetic diseases. Calculation of LOD scores and linkage analysis. Analysis pipelines for next-generation sequencing and clinical applications.

Readings/Bibliography

Suggested course text:

"Genetica Umana e Medica"

Giovanni Neri

Maurizio Genuardi

Edizioni edra

Teaching methods

The course includes a total of 12.5 hours of teaching activities, divided into 8.5 hours of lectures and 4 hours of asynchronous learning activities.

The lectures will be devoted to the systematic presentation of the main course contents, with particular attention to the basic theoretical and methodological aspects of medical genetics.

The asynchronous teaching activities will consist of independent study and in-depth learning activities to be carried out by students using materials made available on the Virtuale platform of the University of Bologna. These activities may include the reading of scientific articles, in-depth documents and study support materials.

The integration of lectures and asynchronous activities aims to promote progressive and autonomous learning, encouraging students to connect theoretical knowledge with the applied contexts of medical genetics.

Assessment methods

Assessment of learning outcomes is carried out through a final written examination designed to evaluate the achievement of the course learning objectives and the acquisition of knowledge in the following areas:

• Molecular Oncology;
• Genetic Pathology;
• Medical Genetics.

The examination is computer-based and takes place on the EOL platform in a computer laboratory. It lasts 90 minutes and consists of the following sections:

• 12 multiple-choice questions, including:
  • 8 questions on molecular oncology;
  • 4 questions on genetic pathology;
• 2 semi-structured questions on medical genetics;
• 2 open-ended questions, one on molecular oncology and one on genetic pathology.

Assessment criteria

Each multiple-choice question is worth 1 point.

Each semi-structured medical genetics question is worth 2 points.

Each open-ended question is worth 8 points.

The maximum total score is 32 points, including 2 additional points that may be awarded for honours. To pass the examination, students must achieve a passing score of at least 5 out of 8 in both open-ended questions. Failure to achieve a passing score in either of the two questions will result in an overall failing grade for the examination.

Since the Medical Genetics questions contribute 4 points to the overall examination score, failure to answer them limits the maximum achievable grade to 26/30, excluding the 2 additional points available for honours.

The examination is passed with a grade of at least 18/30.

The grade awarded represents the overall assessment for the Molecular Pathology course unit, worth 5 CFUcredits, and the Medical Genetics course unit, worth 1 ECTS credit, for a total of 6 CFU credits.

The final grade for the integrated course will be calculated as the weighted average of this grade, worth 6 CFU credits, and the grade obtained in the Immunology course unit, worth 5 CFU credits, according to the following formula:

Final integrated course grade = (Molecular Pathology and Medical Genetics grade × 6 + Immunology grade × 5) / 11

Students with specific learning disabilities or temporary or permanent disabilities are advised to contact the relevant University Office in good time: https://site.unibo.it/studenti-con-disabilita-e-dsa/it .

The Office will propose any necessary accommodations, which must be submitted to the course instructor for approval at least 15 days in advance. The instructor will assess their suitability in relation to the learning objectives of the course.

Teaching tools

Teaching activities will be supported by materials made available through the Virtuale teaching platform, such as lecture slides, scientific articles and in-depth documents.

The teaching tools will be aimed at integrating lectures and asynchronous activities, promoting independent study, the consolidation of knowledge, and the connection between theoretical aspects and medical practice.

Office hours

See the website of Emanuele Panza