Genomic Medicine (HEE Funded) MSc

This module will provide clear understanding of the structure and variations in genetic material. The module aim is to deliver a solid theoretical foundation in the area of basic genetics and genomics to the participants in order to understand the study of disease genetics and how genomic information can be utilised to understand disease mechanisms and biology. The first section 'Genome Structure & Sequence variation' will review the architecture of the human genome and the functional units embedded. It will then cover DNA sequence variation and how it is structured across the genome, explaining the principles of linkage disequilibrium and its extent in human populations. The next part `Biology of Genomes' will cover in more detail aspects of gene regulation (enhancers, promoters, transcription factors, silencers) and chromatin structure (histone modifications; DNase I hypersensitive sites, open chromatin). It will then discuss genetic control of functional elements introducing the basic principles of quantitative trait loci (QTL) analyses. Under the `Association Studies section participants will be introduced to the principles of correlating genetic markers to phenotype as well as the design and execution of association studies both for dichotomous and quantitative traits . Participants will learn how to critically interpret the output of association studies and the potential as well as the limitations of using such information to assess disease risk. Under the Epigenetics section participants will be introduced to DNA methylation and its implication to human disease. In the last section of this module participants will learn about integration of genetic data from an association study with genomic information to explore the biology of the investigated trait.

Module will deliver a comprehensive coverage of the techniques used to obtain the DNA sequence of targeted parts of the genome (e.g. exome sequencing) or whole genomes using state-of -the-art highly parallel sequencing platforms. Furthermore, it will provide clear understanding of the use of array based methodologies and RNA sequencing in estimating expression levels of protein coding genes, micro RNAs and long non-coding RNAs; gene expression is a key intermediate phenotype in genetic / genomic analyses of disease. Finally, the module will offer an introduction to the evolving fields of metabolomics and proteomics covering some of the most established techniques currently used in biomedical research.

Students will learn to handle sequence files from exome and / or whole genome sequencing (e.g. BAM files), apply quality control filters to remove outliers, call variants, annotate variants for functional consequences (e.g. PolyPhene 2 is an algorithm for predicting the impact of amino acid changes on protein stability and function) and finally apply different filtering strategies using publicly available control data sets (e.g. 1000 Genomes Project) to identify pathogenic mutations. The module will cover a wide range of statistical and bioinformatics techniques and tools such as: - R package - PLINK - GATK The module will also cover the use of databases and literature searches to critically assess and annotate findings of genetic and genomic analyses. Theoretical sessions will be coupled with practical assignments of analysing and annotating predefined data sets.