title: Distribution of segmental duplications in the context of higher order chromatin organisation of human chromosome 7.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Grit
authors: G
authors: Ebert
authors: Anne
authors: A
authors: Steininger
authors: Robert
authors: R
authors: Weißmann
authors: Vivien
authors: V
authors: Boldt
authors: Allan
authors: A
authors: Lind-Thomsen
authors: Jana
authors: J
authors: Grune
authors: Stefan
authors: S
authors: Badelt
authors: Melanie
authors: M
authors: Heßler
authors: Matthias
authors: M
authors: Peiser
authors: Manuel
authors: M
authors: Hitzler
authors: Lars R
authors: LR
authors: Jensen
authors: Ines
authors: I
authors: Müller
authors: Hao
authors: H
authors: Hu
authors: Peter F
authors: PF
authors: Arndt
authors: Andreas W
authors: AW
authors: Kuss
authors: Katrin
authors: K
authors: Tebel
authors: Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany. ullmann@molgen.mpg.de.
authors: Reinhard
authors: R
authors: Ullmann
mesh_terms: D000107:Acetylation; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D002889:Chromosomes, Human, Pair 2; D002897:Chromosomes, Human, Pair 7; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D056426:Genetic Loci; D023281:Genomics; D006657:Histones / Q000378:metabolism; D006801:Humans; D056916:Segmental Duplications, Genomic; D014158:Transcription, Genetic; D018980:Williams Syndrome / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones