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Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Chromosome-wise Protein Interaction Patterns and Their Impact on Functional Implications of Large-Scale Genomic Aberrations

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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Vis graf over relationer

Gene copy-number changes influence phenotypes through gene-dosage alteration and subsequent changes of protein complex stoichiometry. Human trisomies where gene copy numbers are increased uniformly over entire chromosomes provide generic cases for studying these relationships. In most trisomies, gene and protein level alterations have fatal consequences. We used genome-wide protein-protein interaction data to identify chromosome-specific patterns of protein interactions. We found that some chromosomes encode proteins that interact infrequently with each other, chromosome 21 in particular. We combined the protein interaction data with transcriptome data from human brain tissue to investigate how this pattern of global interactions may affect cellular function. We identified highly connected proteins that also had coordinated gene expression. These proteins were associated with important neurological functions affecting the characteristic phenotypes for Down syndrome and have previously been validated in mouse knockout experiments. Our approach is general and applicable to other gene-dosage changes, such as arm-level amplifications in cancer.

OriginalsprogEngelsk
TidsskriftCell Systems
Vol/bind4
Udgave nummer3
Sider (fra-til)357-364.e3
ISSN2405-4712
DOI
StatusUdgivet - 22 mar. 2017

ID: 52004627