Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital

Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes

Research output: Contribution to journalJournal articleResearchpeer-review


  1. Genomisk medicin til præimplantations-, 
præ- og postnatal diagnostik

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Risks and Recommendations in Prenatally Detected De Novo Balanced Chromosomal Rearrangements from Assessment of Long-Term Outcomes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Contingent first-trimester screening for aneuploidies with cell-free DNA in a Danish clinical setting

    Research output: Contribution to journalJournal articleResearchpeer-review

  • M N Loviglio
  • M Leleu
  • K Männik
  • M Passeggeri
  • G Giannuzzi
  • I van der Werf
  • S M Waszak
  • M Zazhytska
  • I Roberts-Caldeira
  • N Gheldof
  • E Migliavacca
  • A A Alfaiz
  • L Hippolyte
  • A M Maillard
  • A Van Dijck
  • R F Kooy
  • D Sanlaville
  • J A Rosenfeld
  • L G Shaffer
  • J Andrieux
  • C Marshall
  • S W Scherer
  • Y Shen
  • J F Gusella
  • U Thorsteinsdottir
  • G Thorleifsson
  • E T Dermitzakis
  • B Deplancke
  • J S Beckmann
  • J Rougemont
  • S Jacquemont
  • A Reymond
  • 2p15 Consortium (Susanne Kjærgaard member)
  • Susanne Kjærgaard (Member of study group)
View graph of relations

Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers of the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements are associated with autism spectrum disorders and mirror phenotypes of obesity/underweight and macrocephaly/microcephaly. Such phenotypes were previously associated with rearrangements of the non-overlapping proximal 16p11.2 600 kb BP4-BP5 interval. These two CNV-prone regions at 16p11.2 are reciprocally engaged in complex chromatin looping, as successfully confirmed by 4C-seq, fluorescence in situ hybridization and Hi-C, as well as coordinated expression and regulation of encompassed genes. We observed that genes differentially expressed in 16p11.2 BP4-BP5 CNV carriers are concomitantly modified in their chromatin interactions, suggesting that disruption of chromatin interplays could participate in the observed phenotypes. We also identified cis- and trans-acting chromatin contacts to other genomic regions previously associated with analogous phenotypes. For example, we uncovered that individuals with reciprocal rearrangements of the trans-contacted 2p15 locus similarly display mirror phenotypes on head circumference and weight. Our results indicate that chromosomal contacts' maps could uncover functionally and clinically related genes.Molecular Psychiatry advance online publication, 31 May 2016; doi:10.1038/mp.2016.84.

Original languageEnglish
JournalMolecular Psychiatry
Pages (from-to)836-49
Publication statusPublished - 2017

ID: 49586651