83155 - Medical Genetics

Learning outcomes

Discuss the impact of human genome projects on genetic medicine. Identify the major categories of genetic disorders, and describe differences in their etiology and inheritance pattern. Reconstruct family pedigrees, and apply the principles of mendelian inheritance and population genetics to estimate the risk of recurrence of a monogenic disease. Describe the impact of variations to Mendelian inheritance on the clinical presentation of inherited disorders. Identify the clinical manifestations and etiology of selected genetic conditions, through critical analysis of clinical cases. Define the role of genetic counselling in the management of inherited diseases.

Course contents

Genetic disorders

• classes of genetic disorders
• genetic counseling: indications, purpose, process
  
• review of genetic testing, genomic variation and clinical interpretation genetic variants
  
• 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 (presented with disease examples)

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

Mendelian disorders

• Achondroplasia
• 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

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
• In-class Wooclap activitites
• problem-based learning: human genetics problems to be solved in class with active student participation

Assessment methods

Medical Genetics unit:

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

Assessment will be carried out in two steps:

1) End-of-course assignment: students are asked to write a brief essay on a hereditary disorder of their choice, following guidelines that will be provided. The essay must be submitted to the professor 7 days before the official Integrated Course exam.

The assignment will contribute 50% of the Medical Genetics assessment based on the following criteria: 1) content accuracy and completeness, 2) organization and clarity of presentation, and 3) source of information and resources used. 

2) Oral exam: the student will be invited to discuss the content of the written essay and answer relevant questions on the chosen disorder in order to demonstrate understanding of the topic. The student may also be asked additional question(s) on the course content and/or resolve a medical genetics problem (e.g. pedigree interpretation, risk assessment, carrier frequency calculation).

The oral exam will contribute 50% of the medical genetics assessment, which will be held on the date of the Pediatrics Integrated Course exam session published in AlmaEsami.

Pediatrics Integrated Course

The final grade awarded for the Integrated 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.

Grading scale

Final grades will be assigned according to the following criteria:

• 30/30L (Outstanding): full preparation, consolidated and without inaccuracies on the topics covered in the integrated course. Ability to promptly frame the topic. Ability to analyze and connect independently different topics. Concepts in the right succession and full command of the specific language with some original elaboration by the student.
• 29-30/30 (Excellent): full preparation, consolidated and without significant inaccuracies on the topics covered in the course. Ability to promptly frame the topic. Ability to analyze and connect independently. Concepts in the right succession and full command of the specific language.
• 27-28/30 (Very good): preparation of very good level, but with significant inaccuracies compromising the achievement of full marks. Ability to analyze and link independently. Exposure of concepts in the right succession and with appropriate language.
• 23-26/30 (Good): preparation of good level, but with important inaccuracies in the presentation. Ability to analyze and link after input from the teacher. Exposure of concepts in the right succession and with appropriate language.
• 18-22/30 (Sufficient): knowledge limited to the basic concepts without serious gaps, only after input from the teacher. Exposition of concepts and language acceptable as a whole.
• <18/30 (Insufficient/fail): lack of preparation. Serious and repeated conceptual errors.

Teaching tools

The following material will be available online through Virtuale:

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

Office hours

See the website of Kerry Jane Rhoden