Medical Genomics

COURSE OBJECTIVE
1. The student has knowledge of essential methods in genomics and understands the suitability and limitations of those methods, given a
scientific goal. These methods comprise: Genome mapping & sequencing, Exome & RNA sequencing, Karyotyping, Comparative Genomic Hybridization, Expression profiling with microarrays or ‘Gene Chips’, Proteomics, Metabolomics, SNP arrays, non-invasive prenatal testing.
2. The student can identify and describe various types of genetic variation within a natural population (SNPs, CNVs, repeats and other
types of genetic markers) and can derive the inheritance pattern of genetic traits from a pedigree. He/she understands how the heritability
of a trait can be measured, how monogenetic disease genes can be identified by haplotyping and linkage analysis, and how quantitative
trait loci and complex disease genes can be identified.
3. The student is familiar with the properties of important genetic model organisms including yeast, nematodes, fruit flies and mice and can
choose the most suitable organism for a scientific problem. He/she can explain how breeding strategies can be used to control genetic variation and how these strategies can be applied in research.
4. The student is familiar with important methods for genetic manipulation including transgenesis, homologous gene targeting, RNA
interference and genome editing and can write a research strategy describing an effective approach for a given scientific aim.
5. The student can collect relevant information from public databases (genome browsers, gene, transcript and protein sequence databases, 3D structures, OMIM, PubMed) and apply the resulting information to solve medical and biological problems.
6. The student can interpret genetic literature where the aforementioned methods (see 1-4) are applied and present the key message to his/her peers.
7. The student can reflect on the application of methods in medical genomics in health care and discuss their potential impact on future
health care. Such applications include gene therapy, stem cell therapy, drug design and development, clinical diagnostics and genetic
counselling.

COURSE CONTENT
At the start of the course, a basic knowledge of molecular biology or genetics is assumed. Key facts will be recapitulated in the chapter
“Molecular Biology Basics” for the purpose of memory refreshment. The structural organization of the genome in prokaryotic and eukaryotic
organisms will be described.

Similarity comparisons between genomes from different species can yield information about evolutionary changes and relate observations in different organisms. This approach is referred to as “Comparative Genomics”. Certain species have become model organisms in genomics research; these will be introduced together with their individual strengths and weaknesses.

To find relevant pieces of information in publicly available databases, a proper use of similarity search algorithms is required. The most
important algortithms are BLAST or BLAT search tools. You will develop skills in using these tools in various assignments. In addition,
analysis of the genome and its products requires many other special tools and techniques. Methods are described to study the transcriptome (in the form of mRNA), the proteome (in the form of proteins) and the metabolome (in the form of chemical compounds made by enzymes).

When focusing on the human genome, powerful approaches have been developed to identify the location and identity of disease genes.
Different modes of inheritance (e.g. Mendelian or complex)require different approaches for successful disease gene finding. These
approaches are summarized in the chapters “Mendelian Genetics” and “Complex Trait Genetics“.

For final confirmation of the causal involvement of a disease gene mutation in an associated phenotype, genome manipulation is often
performed in model organisms (e.g. mice). The resulting animal model can subsequently be used to study the disease’s pathogenesis and to develop treatment options. In this context, it is also important to consider ethical and legal aspects of genetic manipulation, working with
experimental animals, stem cell technology and other applications of medical genomics.

TEACHING METHODS
The course comprises of lectures (~40 h) and workgroups (~15 h). In addition, approximately 120 h of self study is expected. THe lectures (optional but highly recommended) will cover complete theory providing a basis for many concepts and methods in medical genomics. The workgroups (for which participation is obligatory) will emphasize how these methods can be applied in health care or biomedical research.

TYPE OF ASSESSMENT
The final grade is composed of two parts. To pass for the course, both parts must be completed with a 5.5 or higher.

First, the full course theory will be assessed by a multiple choice digital exam at the end of the course. This test will contribute 60% to the final grade.

Second, the performance in workgroup assignments will collectively count for 40% of the final grade. These assignments inlcude oral presentations, group discussions and written assignments.