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: Lectures

• Sequencing the human genome: international projects (HGP, HapMap, 1000Genomes, Exome); sequencing technologies (from Sanger sequencing to NGS)
• Medical genetics: classes of genetic diseases, elements of genetic counseling and molecular diagnostics, pedigrees, mendelian and non-mendelian inheritance patterns, risk calculation, Hardy-Weinberg principle
• Identification of disease genes: pre- and post-genomic strategies, genetic markers, mapping, analysis of linkage,
• Mendelian diseases: autosomal dominant (Huntigton disease, Marfan Syndrome, achondroplasia, osteogenesis imperfecta), autosomal recessive (cystic fibrosis), X-linked recessive (Duchenne's muscular dystrophy); variations of mendelian inheritance (variable expressivity, genetic heterogeneity, incomplete penetrance, anticipation, germinal mosaicism, X-inactivation, oligogenic inheritance, genomic imprinting)
• Chromosomal diseases: classical and molecular cytogenetics, numerical and structural chromosomal abnormalities, genomic disorders, UPD, Angelman and Prader-Willie Syndromes
• Mitochondrial diseases
• Multifactorial diseases: heritability, susceptibility genes, polymorphisms, high throughput genotyping, GWAS
• Pharmacogenomics and personalized medicine

Module 2: Laboratory

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

• The course will be divided in two parts: a wet-lab course, where the students will prepare PCR and sequencing reactions, and a part using informatics tools, including public programs and databases, in order to analyze the obtained sequences and evaluate the presence of variants/mutations and determine their possible pathogenicity.

Readings/Bibliography

Reading material will be provided through Insegnamenti OnLine, 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:

• frontal lectures with PowerPoint slides
• class-room excercises on human genetics: interpretation of pedigrees for the assessment of inheritance patterns, risk calculation, using the Hardy-Weinberg principle to calculate the frequency of carriers in a population, identification of recombinant/non-recombinant genotypes, interpretaion of LOD scores
• presentation by groups of students of original research articles on topics related to lectures
• practical molecular genetics wet-lab in groups
  
• use of bioinformatics tools, including public programs and databases
  

Students are expected to participate actively in all activities.

Assessment methods

• Written exam in english consisting of multiple choice questions, true/false questions and human genetics excercises
• Students have the option of supplementing the writtan exam with an oral exan in english

Teaching tools

• Classroom with PC and projector
• Teaching laboratory
• Bioinformatics classroom equipped with individual computers
  

Office hours

See the website of Kerry Jane Rhoden

See the website of Elena Bonora