English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Deletions of chromosomal regulatory boundaries are associated with congenital disease

Ibn-Salem, J., Köhler, S., Love, M. I., Chung, H.-R., Huang, N., Hurles, M. E., et al. (2014). Deletions of chromosomal regulatory boundaries are associated with congenital disease. Genome Biology: Biology for the Post-Genomic Era, 15: 15:423. doi:10.1186/s13059-014-0423-1.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-1FC9-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-77EC-3
Genre: Journal Article

Files

show Files
hide Files
:
Ibn-Salem.pdf (Publisher version), 2MB
Name:
Ibn-Salem.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2014 Ibn-Salem et al.; licensee BioMed Central Ltd
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Ibn-Salem, J., Author
Köhler, S., Author
Love, M. I.1, Author              
Chung, H.-R.2, Author              
Huang, N., Author
Hurles, M. E., Author
Haendel, M., Author
Washington, N. L., Author
Smedley, D., Author
Mungall, C. J., Author
Lewis, S. E., Author
Ott, C. E., Author
Bauer, S., Author
Schofield, P. N., Author
Mundlos, S.3, Author              
Spielmann, M.3, Author              
Robinson, P. N., Author
Affiliations:
1IMPRS for Computational Biology and Scientific Computing - IMPRS-CBSC (Kirsten Kelleher), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479666              
2Computational Epigenetics (Ho-Ryun Chung), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479658              
3Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              

Content

show
hide
Free keywords: -
 Abstract: BACKGROUND: Recent data from genome-wide chromosome conformation capture analysis indicate that the human genome is divided into conserved megabase-sized self-interacting regions called topological domains. These topological domains form the regulatory backbone of the genome and are separated by regulatory boundary elements or barriers. Copy-number variations can potentially alter the topological domain architecture by deleting or duplicating the barriers and thereby allowing enhancers from neighboring domains to ectopically activate genes causing misexpression and disease, a mutational mechanism that has recently been termed enhancer adoption. RESULTS: We use the Human Phenotype Ontology database to relate the phenotypes of 922 deletion cases recorded in the DECIPHER database to monogenic diseases associated with genes in or adjacent to the deletions. We identify combinations of tissue-specific enhancers and genes adjacent to the deletion and associated with phenotypes in the corresponding tissue, whereby the phenotype matched that observed in the deletion. We compare this computationally with a gene-dosage pathomechanism that attempts to explain the deletion phenotype based on haploinsufficiency of genes located within the deletions. Up to 11.8% of the deletions could be best explained by enhancer adoption or a combination of enhancer adoption and gene-dosage effects. CONCLUSIONS: Our results suggest that enhancer adoption caused by deletions of regulatory boundaries may contribute to a substantial minority of copy-number variation phenotypes and should thus be taken into account in their medical interpretation.

Details

show
hide
Language(s): eng - English
 Dates: 2014-07-242014-09-04
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1186/s13059-014-0423-1
ISSN: 1465-6906 (Electronic)
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Genome Biology : Biology for the Post-Genomic Era
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: London : BioMed Central Ltd.
Pages: - Volume / Issue: 15 Sequence Number: 15:423 Start / End Page: - Identifier: ISSN: 1465-6906
CoNE: /journals/resource/1000000000224390