1.9 Structure of this thesis

The following four chapters address and discuss the questions raised above. First, the focus is on duplicated genes in the human genome. Because of their related sequences and functions, a shared evolutionary history, and close colocalization in the genome they represent an interesting model to study how genome folding is related to regulation of gene expression during evolution (Chapter 2). Next, whole-genome alignment between human and other vertebrate genomes are used to systematically investigate whether TADs represent conserved building blocks of genomes and whether rearrangements of TADs lead to altered gene expression programs (Chapter 3). Then, we address disruptions of chromatin organization by analyzing disease associated rearrangement breakpoints from whole-genome sequenced patients of various genetic disorders to explain their phenotypes by miss-regulation of genes in disrupted TADs (Chapter 4). Finally, we make use of recent insights in chromatin loop formation to provide a computational tool for predicting long-range chromatin contacts from broadly available ChIP-seq data, with the aim to facilitate three-dimensional folding analysis in diverse tissues and conditions for which Hi-C like data is not available (Chapter 5). The overall findings are then discussed in the context of most recent literature and future research perspectives (Chapter 6).