81594 - Medical Genomics-

Learning outcomes

Identify the major categories of inherited diseases, the genetic mechanisms contributing to disease etiology, and their inheritance patterns. Describe strategies to identify the genetic causes of inherited diseases. Discuss the use of genomic data and technology in the management of inherited diseases. Discuss innovations in human genomic research and their applications in medicine. Critically evaluate research articles pertinent to medical genomics.

Course contents

Module 1 (Prof. Rhoden)

Students will acquire knowledge and skills in medical genetics and genomics. Specific topics include:

• Introduction to medical genomics: review of genomic variation, human genome sequencing projects.
  
• Principles of medical genetics: classes of genetic diseases, overview of genetic counseling and genetic testing, online resources.
  
• Mendelian inheritance: autosomal and X-linked inheritance patterns, risk of recurrence, Hardy-Weinberg equilibrium.
• Exceptions to mendelian inheritance: de novo mutations, incomplete penetrance, variable expressivity, triplet expansion and anticipation, genetic heterogeneity, allelic disorders, digenic inheritance, irregularities of X-linked inheritance, digenic inheritance.
• Mendelian diseases: achondroplasia, Huntington disease, osteogenesis imperfecta, Marfan Syndrome, cystic fibrosis, Duchenne's muscular dystrophy.
  
• Mendelian disease gene identification: gene mapping, analysis of linkage, autozygosity mapping, haplotype analysis, pre-genomic strategies (functional, candidate, positional cloning), whole exome sequencing.
• Chromosomal disorders: cytogenetic techniques, polyploidy, anauploidy, structural anomalies, genomic disorders.
  
• Genomic impring and uniparental disomy: Angelman syndrome, Prader-Willie syndrome.
  
• Mitochondrial diseases: maternal inheritance, mitochondrial DNA, heteroplasmy, mitochondrial threshold, mitochondrial bottleneck
  
• Multifactorial/complex disorders: susceptibility genes, gene-environment interation, liability threhold model, heritability, familial aggregation, twin concordance, adoption studies, association studies, linkage disequilibrium, GWAS
  
• Pharmacogenomics: variation in drug efficacy and adverse drug reactions; pharmacokinetic variation in drug metabolism (CYP2D6) and transport (SLCO1B1 and statin therapy); pharmacodynamic variation (beta-agonists and asthma therapy); polygenic variation (warfarin anticoagulant therapy.

Attention will be given to present recent advances described in the scientific literature which illustrate the application and impact of genomic technology on our current understanding of inherited disorders.

Module 2 Laboratory (Prof. Bonora)

• Students will acquire essential knowledge and skills to design and perform molecular genetics experiments, including PCR and Sanger sequencing, to evaluate the presence of variations/mutations in human DNA and their role in Mendelian disorders.

• The module will be divided into three parts: (i) lectures outlining technologies (Sanger sequencing, next generation sequencing, array CGH) and bioninformatic tools, (ii) practical wet-lab in which students will prepare PCR and sequencing reactions, and (iii) bioinformatic analysis with publicly-available programs and databases in order to analyze the obtained sequences, evaluate the presence of variants/mutations and determine their possible pathogenicity.

Readings/Bibliography

Reading material will be provided online through Virtuale, including:

• pdf files of lectures
• original research articles and reviews on selected topics

Students are also encouraged to consult the following textbooks to supplement information provided in lectures:

• Human Molecular Genetics. Tom Strachan and Andrew Read. Garland Science.
• Thompson and Thompson Genetics in Medicine. Robert L. Nussbaum, Roderick R. McInnes, and Huntington F. Willard. Saunders/Elsevier.

Teaching methods

The course will use both lecture-based teaching methods and active learning approaches:

• lectures with PowerPoint slides
• problem-based learning: human genetics excercises including pedigrees interpretation, risk calculation, carrier frequency calculation using the Hardy-Weinberg equation, identification of recombinant/non-recombinant genotypes, interpretation of LOD scores
  
• practical molecular genetics wet-lab in groups
  
• use of bioinformatics tools, including publicly-available programs and databases (own computer required)
  

Students are expected to participate actively in all activities.

Assessment methods

Medical Genomics

• Computer-based written exam using EsamiOnline with 16 multiple choice questions (5 possible answers, one correct) covering topics addressed in both Medical Genomics modules (14 questions for Module 1 and 2 questions for Module 2).
• Questions may include exercises (pedigree intepretation; calculations of recurrence risk, carrier frequency, recombination frequency etc.). Calculators are allowed.
  
• Three exam dates will be published for the written exam (one in June, one in July, one in September); students can sit the exam twice, choosing 2 out of 3 published dates. The highest score obtained by the student will be used for the final assessment of the Integrated Course.

Integrated Course

• The grade for the Integrated Course will be calculated as the mean of grades obtained in written exams for Medical Genomics and Classical and Next Generation Genomics.
• Three dates will be published for the official validation of Integrated Course grades (one in June, one in July, one in September); additional dates will be published if needed.
• Students who fail one or both written exam(s) for Medical Genomics and Classical and Next Generation Genomics must take an oral exam for the entire Integrated Course on one of three published dates.
• All students have the option of taking the oral exam for the Integrated Course to aim for a better grade. In this case, however, the grades obtained previously in written exams will no longer be held valid.

Teaching tools

• Teaching laboratory
  
• Online resources: Wooclap, bioinformatic tools and databases
  

Office hours

See the website of Kerry Jane Rhoden

See the website of Elena Bonora