Human Monogenic Diseases

Content

GENES AND GENOMES

Credit load: 7.5 ECTS                                                       Course code: BMW20605
Coordinator: Dr. B.P.C. Koeleman                                   Period: 3
Examiner: Dr. B.P.C. Koeleman                                       Timeslot: BC
E-mail address: b.p.c.koeleman@umcutrecht.nl           Level: 2
Phone: +31 88 756 8297           
 
Content:  
Organisation and evolution of genomes and genes
General organisation of the genome of higher eukaryotes

• Comparative genomics and genome annotation. Special attention for gene structure, gene duplication, molecular phylogeny, genome analysis, species comparisons and useful software and databases.
• Functional genomics, including functional annotation of genes, gene expression, proteomics.
• We pay attention to how knowledge is obtained, and how information can be extracted from existing sources.

Identification of mutations that influence human diseases

• Linkage analysis in families with a monogenic disease to localise the causal variant up to a region of ca 15 cM/
• Laboratory aspects of DNA research: the techniques, their interpretation and the causes of artefacts
• Positional cloning/Prioritising genes within a defined region. Mutation analysis; the role of new technology.
• Molecular pathology: how mutations change phenotypes, and how to prove it.

 
Requirements for admission:
We require the students to have knowledge of the structure and organisation of DNA; the processes of meiosis and mitosis, including recombination; transcription and translation; gene expression. In addition we ask for some basic knowledge of laboratory techniques such as PCR, restriction enzymes and DNA-hybridisation. In case of deficiencies, contact the coordinator for background reading to be done before the start of the course.
 
Learning outcomes:
Knowledge & Insight
After completing this course, the student will be able to:

• Reproduce the organisation of the human genome in approximate numbers
• Explain how genome projects have contributed to our current knowledge of the influence of genes on traits
• Describe the steps with which genomes are characterized
• Describe approaches that help us understand the function of genes
• Understand the value and drawbacks of species comparisons in genetic studies
• Explain the principles of linkage analysis, and use this method for simple cases.
• Choose appropriate molecular techniques for different purposes
• Interpret the link between mutation and disease

 
Skills
After completing this course, the student will be able to:

• Use genome data, gene data and functional data from existing sources to interpret new data in the process of identifying a mutation that might be causing a disease
• Apply comparative genomics with the appropriate software
• Apply and understand the law of Hardy-Weinberg

 
Academic Skills

• Read academic articles with a critical mind
• Combine information from different sources
• Write a report according to academic standards
• Orally present your work, and formulate questions about other people’s oral presentations
• Collaborate in such a way that the best possible group effort is achieved

 
 
Teaching forms and contact time:
Knowledge and skills are mainly taught in three different forms: in lectures, during exercises and in the textbook. These three forms overlap only partially: information is often only presented in one form. During the first eight weeks, each week a new topic is introduced by a specialised teacher. In the fifth week, students start working in groups on an essay, which will be handed in on paper, as well presented orally. During the last two weeks, the students can devote all their time to this essay. The work on this essay will help processing and integrating the material presented during the course. It will also serve to practice academic skills.
 
On average, about six hours of contact time per week.
 
Method(s) of testing:
The final grade is composed of the results of two tests, a database assignment, the essay and the oral presentation of the essay. Passing the course requires: 5,5 as final grade, but also 5,5 as weighted average of the two tests.
 
Required material:

• Textbook: Human Molecular Genetics, T. Strachan and A. P. Read 4^th edition, Garland Science, 2010, ISBN 0815341490;

Access to Blackboard