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Proteome dysregulation in Down syndrome reveals organelle specific aberrations

ABSTRACT: Human Trisomy 21 (T21), which causes Down Syndrome (DS), is the most common known cause of intellectual disability. However, the molecular basis for DS phenotypic variability remains poorly understood. Here we used SWATH mass spectrometry (SWATH-MS) to quantify protein abundance and protein turnover in fibroblasts from a monozygotic twin pair discordant for T21, and to profile protein expression in 11 unrelated DS individuals and age-matched controls. The integration of the steady state and turnover proteomic data sets with transcript profiles indicated that protein-specific degradation of members of stoichiometric complexes presents a major determinant of T21 gene dosage outcome, a primary effect that was not apparent from genomic data. The data also reveal that T21 results in extensive proteome remodeling similarly affecting proteins encoded by all chromosomes. Finally, we found broad, organelle-specific posttranscriptional effects such as significant down-regulation of the mitochondrial proteome contributing DS hallmarks and variability.

INSTRUMENT(S): TripleTOF 5600, LTQ Orbitrap Elite, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Skin, Fibroblast

SUBMITTER: Yansheng Liu

LAB HEAD: Ruedi Aebersold

PROVIDER: PXD004880 | Pride | 2017-11-01

REPOSITORIES: Pride

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			Action	DRS
	20150611_PB_twins.raw	Raw
	20150611_PB_unrelated.raw	Raw
	20150612_PB_YL_twin_pH03.raw	Raw
	20150612_PB_YL_twin_pH04.raw	Raw
	20150612_PB_YL_twin_pH05.raw	Raw

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