New techniques to detect genomic variation

Abstract

Variation in structure and composition of the DNA are found throughout our genome. All types of variation are collectively called __genomic variation__. Identification and analysis of genomic variation is important to distinguish neutral variants (__non pathogenic__) from variants involved in disease (__pathogenic__). Identification of new disease genes will increase our knowledge of the molecular pathogenesis of genetic disorders. Every technical advance in genetic analysis has revealed new levels of variation, ranging from single nucleotide differences to full chromosome changes. As new DNA methods are applied, increasing numbers of variants with unclear significance to disease (UVs) are identified and choices have to be made regarding the variants that deserve follow-up work. When the pathogenic consequence of a variant is unclear, the effect has to be studied in detail at other levels (functional studies, RNA studies, in silico analysis tools, and databases). The research described in this thesis outlines the rapid development and application of molecular techniques for detecting (pathogenic) genomic variation in the context of genetic disorders.