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Understanding the epigenome using system genetics 10.17863/CAM.15988 Timmer, Sander Willem Genetics has been successful in associating DNA sequence variants to both dichotomous and continuous traits in a variety of organisms, from plant and farm animal studies to human disease. With the advent of high-throughput genotyping, there has been an almost routine gen- eration of genome-wide association studies (GWAS) between human disease traits and genomic regions. Despite this success, a particular frustration is that the majority of associated loci are in non-coding regions of the genome and thus interpretation is hard. To improve characterisation of non-coding regions, molecular as- says can be used as a phenotype, and subsequently be used to explain how genetics alter molecular mechanisms. In this thesis, the inter- play of three molecular assays that are involved in regulating gene expression is studied. On 60 individuals, several assays are performed: FAIRE-chip, CTCF- seq, RNA-seq and DNA-seq. In the first part, the discovery and characteristics of FAIRE-QTLs is presented. The identified FAIRE-QTLs show strong overlap with other molecular QTLs, histone modifications, and transcription factors. The second part consists of the integration of genome-wide molecu- lar assays in a human population to reconstruct the human epigenome. Each of the molecular assays is associated with each of the other assays to discover phenotype-to-phenotype correlations. Furthermore, QTL data are used to dissect the causality for these phenotype-to-phenotype correlations in a system genetic manner. The third part presents a comprehensive view of CTCF binding on the X chromosome, and its implications for X-chromosome inactivation. A novel X chromosome-wide CTCF effect is observed. Using the gender of each of the cell lines, observations are made about which CTCF sites are dosage-compensated, active on both chromosomes, or are only bound in females. University of Cambridge 2015-01-06 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/246693 https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/c6b0ab5e-c9cd-499f-8ff6-cb6194581f33/download 5009ba98fe7c0a15e534ebd4e0be6ee4 https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/ca782970-145f-4d0b-894e-38d1c0de09ae/download 835269bda140c10400fe0606a14c3d21 genetics epigenetics gwas dna gene regulation