Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT
Zur Ablage hinzufügen
  Lokale TagsFreigabegeschichteDetailsÜbersicht

Freigegeben
Zeitschriftenartikel

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

MPG-Autoren
/persons/resource/persons244922

Melo,  Uirá Souto
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons194839

Schöpflin,  Robert
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

Acuna-Hidalgo,  Rocio
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

Fischer-Zirnsak,  Björn
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

Klever,  Marius-Konstantin
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons179829

Heinrich,  Verena
Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50613

Vingron,  Martin
Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50369

Kalscheuer,  Vera
Chromosome Rearrangements and Disease (Vera Kalscheuer), Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50565

Spielmann,  Malte
Human Molecular Genomics (Malte Spielmann), Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50437

Mundlos,  Stefan
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

Externe Ressourcen
Es sind keine externen Ressourcen hinterlegt
Volltexte (beschränkter Zugriff)
Für Ihren IP-Bereich sind aktuell keine Volltexte freigegeben.
Volltexte (frei zugänglich)
Es sind keine frei zugänglichen Volltexte in PuRe verfügbar
Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

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.


Zitierlink: https://hdl.handle.net/21.11116/0000-0007-67CB-1
Zusammenfassung
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.