Open Access Open Badges Research article

Distribution of segmental duplications in the context of higher order chromatin organisation of human chromosome 7

Grit Ebert12, Anne Steininger12, Robert Weißmann3, Vivien Boldt12, Allan Lind-Thomsen4, Jana Grune1, Stefan Badelt15, Melanie Heßler1, Matthias Peiser6, Manuel Hitzler6, Lars R Jensen3, Ines Müller1, Hao Hu1, Peter F Arndt1, Andreas W Kuss3, Katrin Tebel1 and Reinhard Ullmann1*

Author Affiliations

1 Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany

2 Department of Biology, Chemistry and Pharmacy, Free University Berlin, 14195 Berlin, Germany

3 Department of Human Genetics, University Medicine Greifswald, and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Fleischmannstraße 42-44, 17475 Greifswald, Germany

4 Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark

5 Current address: Institute for Theoretical Chemistry, University of Vienna, Waehringer Straße 17, A-1090 Vienna, Austria

6 Unit Experimental Research, Department of Product Safety, Federal Institute for Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Neuherbergstraße 11, 80937 Munich, Germany

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BMC Genomics 2014, 15:537  doi:10.1186/1471-2164-15-537

Published: 29 June 2014



Segmental duplications (SDs) are not evenly distributed along chromosomes. The reasons for this biased susceptibility to SD insertion are poorly understood. Accumulation of SDs is associated with increased genomic instability, which can lead to structural variants and genomic disorders such as the Williams-Beuren syndrome. Despite these adverse effects, SDs have become fixed in the human genome. Focusing on chromosome 7, which is particularly rich in interstitial SDs, we have investigated the distribution of SDs in the context of evolution and the three dimensional organisation of the chromosome in order to gain insights into the mutual relationship of SDs and chromatin topology.


Intrachromosomal SDs preferentially accumulate in those segments of chromosome 7 that are homologous to marmoset chromosome 2. Although this formerly compact segment has been re-distributed to three different sites during primate evolution, we can show by means of public data on long distance chromatin interactions that these three intervals, and consequently the paralogous SDs mapping to them, have retained their spatial proximity in the nucleus. Focusing on SD clusters implicated in the aetiology of the Williams-Beuren syndrome locus we demonstrate by cross-species comparison that these SDs have inserted at the borders of a topological domain and that they flank regions with distinct DNA conformation.


Our study suggests a link of nuclear architecture and the propagation of SDs across chromosome 7, either by promoting regional SD insertion or by contributing to the establishment of higher order chromatin organisation themselves. The latter could compensate for the high risk of structural rearrangements and thus may have contributed to their evolutionary fixation in the human genome.

Higher order chromatin organisation; Segmental duplication; Williams-Beuren syndrome; Chromosome evolution; Hi-C