English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Hi-C Identifies Complex Genomic Rearrangements and TAD-Shuffling in Developmental Diseases

Melo, U. S., Schöpflin, R., Acuna-Hidalgo, R., Mensah, M. A., Fischer-Zirnsak, B., Holtgrewe, M., et al. (2020). Hi-C Identifies Complex Genomic Rearrangements and TAD-Shuffling in Developmental Diseases. The American Journal of Human Genetics, 106(6), 872-884. doi:10.1016/j.ajhg.2020.04.016.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0007-67CB-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-67CC-0
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Melo, Uirá Souto1, Author              
Schöpflin, Robert1, Author              
Acuna-Hidalgo, Rocio1, Author
Mensah, Martin Atta, Author
Fischer-Zirnsak, Björn1, Author
Holtgrewe, Manuel, Author
Klever, Marius-Konstantin1, Author
Türkmen, Seval, Author
Heinrich, Verena2, Author              
Datkhaeva Pluym, Ilina , Author
Matoso, Eunice , Author
de Sousa, Sérgio Bernardo , Author
Louro, Pedro , Author
Hülsemann, Wiebke, Author
Cohen, Monika , Author
Dufke, Andreas , Author
Latos-Bieleńska, Anna , Author
Vingron, Martin2, Author              
Kalscheuer, Vera3, Author              
Quintero-Rivera, Fabiola , Author
Spielmann, Malte4, Author              Mundlos, Stefan1, Author               more..
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              
2Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              
3Chromosome Rearrangements and Disease (Vera Kalscheuer), Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385702              
4Human Molecular Genomics (Malte Spielmann), Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3014183              

Content

show
hide
Free keywords: Hi-C topologically associating domains gene misregulation developmental disorders cytogenetics neo-TAD chromosome conformation capture ectopic enhancer-promoter interactions
 Abstract: Genome-wide analysis methods, such as array comparative genomic hybridization (CGH) and whole-genome sequencing (WGS), have greatly advanced the identification of structural variants (SVs) in the human genome. However, even with standard high-throughput sequencing techniques, complex rearrangements with multiple breakpoints are often difficult to resolve, and predicting their effects on gene expression and phenotype remains a challenge. Here, we address these problems by using high-throughput chromosome conformation capture (Hi-C) generated from cultured cells of nine individuals with developmental disorders (DDs). Three individuals had previously been identified as harboring duplications at the SOX9 locus and six had been identified with translocations. Hi-C resolved the positions of the duplications and was instructive in interpreting their distinct pathogenic effects, including the formation of new topologically associating domains (neo-TADs). Hi-C was very sensitive in detecting translocations, and it revealed previously unrecognized complex rearrangements at the breakpoints. In several cases, we observed the formation of fused-TADs promoting ectopic enhancer-promoter interactions that were likely to be involved in the disease pathology. In summary, we show that Hi-C is a sensible method for the detection of complex SVs in a clinical setting. The results help interpret the possible pathogenic effects of the SVs in individuals with DDs.

Details

show
hide
Language(s): eng - English
 Dates: 2020-06-04
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.ajhg.2020.04.016
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: The American Journal of Human Genetics
  Other : Am. J. Hum. Genet.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: American Society of Human Genetics
Pages: 13 Volume / Issue: 106 (6) Sequence Number: - Start / End Page: 872 - 884 Identifier: ISSN: 0002-9297
CoNE: https://pure.mpg.de/cone/journals/resource/954925377893_1