81594 - MEDICAL GENOMICS-

Conoscenze e abilità da conseguire

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.

Contenuti

Module 1 (Prof. Rhoden)

Students will acquire knowledge and skills in medical genetics and genomics. 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.

Specific topics include:

• Introduction to genetic diseases: classes of genetic disorders; elements of genetic counselling; pedigree reconstruction; genetic testing purpose and strategies; online resources.
• Mendelian inheritance: review of inheritance patterns (autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive), risk of recurrence, Hardy-Weinberg principle, carrier frequency calculation.
• Irregularities of mendelian inheritance: de novo mutations, mosaicism, incomplete penetrance, variable expressivity, genetic and allelic heterogeneity, allelic disorders, pseudoautosomal inheritance, male lethality, X chromosome inactivation, repeat expansion. Disease examples include acondroplasia, neurofibromatosis, osteogenesis imperfecta, hearing loss, Huntington disease and Duchenne muscular dystrophy.
• Focus on cystic fibrosis: clinical manifestations, pathophysiology, genetics, targeted therapy
• Gene mapping: analysis of linkage
• Pre-and post-genomic strategies for the indentifiction of mendelian disease genes: functional cloning, positional cloning, in silico data mining, NGS strategies
• Mitochondrial disorders:  mitochondrial DNA, maternal inheritance, heteroplasmy and threshold effect, mitochondrial bottleneck
• Chromosomal abnormalities and structural variation: aneuploidy, polyploidy, structural rearrangements; contiguous gene disorders (CATCH22 deletion syndrome); structural variation, copy number variation
  
• Genomic imprinting and uniparental disomy: Angelman syndrome, Prader-Willi syndrome
  
• Multifactorial/complex inheritance: susceptibility genes, liability threshold model, familial aggregation, twin concordance, adoption studies, linkage disequilibrium, association studies, GWAS, polygenic risk score
• Pharmacogenetics and pharmacogenomics: variable drug responses, adverse drug reactions, pharmacogenes, drug metabolism (focus on CYP2D6), drug transport (focus on SLC1B1 and statin therapy), warfarin pharmacogenomics, genotype-guided therapy, online resources.

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.

Testi/Bibliografia

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.

Note: previous editions of both textbooks will also be available on Virtuale as pdf files

Metodi didattici

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

• traditional lectures with PowerPoint slides
• problem solving with the aid of Wooclap in class and at home
  
• 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 in all activities.

Modalità di verifica e valutazione dell'apprendimento

Medical Genomics

• Computer-based written exam using EsamiOnline with 16 multiple choice questions covering topics addressed in both Medical Genomics modules (14 questions for Module 1 and 2 questions for Module 2).
• Questions may include problems to be solved (e.g. interpret a pedigree; calculate the risk of recurrence, carrier frequency or recombination frequency). 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.
  

Strumenti a supporto della didattica

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

Orario di ricevimento

Consulta il sito web di Kerry Jane Rhoden

Consulta il sito web di Elena Bonora