Pathogenicity of genomic duplications is determined by formation of novel chromatin domains (neo-TADs) (4C-seq)

Genome-scale methods have identified subchromosomal structures so-called topologically associated domains (TADs) that subdivide the genome into discrete regulatory units, establish with their target genes. By re-engineering human duplications at the SOX9 locus in mice combined with 4C-seq and Capture Hi-C experiments, we show that genomic duplications can result in the formation of novel chromatin domains (neo-TADs) and that this process determines their molecular pathology. Overall design: Circular Chromosome Conformation Capture (4C seq) and Capture Hi-C experimetns at the Sox9/Kcnj locus in developing distal limbs of mutants and WT animals at E12.5 as well as from patient fibroblasts