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Determining Allele-Specific Protein Expression (ASPE) Using a Novel Quantitative Concatamer Based Proteomics Method.

Jian Shi1, Xinwen Wang1, Huaijun Zhu1,2

  • 1Department of Clinical Pharmacy , University of Michigan , Ann Arbor , Michigan 48109 , United States.

Journal of Proteome Research
|August 25, 2018
PubMed
Summary
This summary is machine-generated.

A new targeted proteomics method quantifies allele-specific protein expression (ASPE), revealing cis-regulatory variants impacting post-transcription. This technique advances the study of genetic variations affecting gene expression post-translation.

Keywords:
ASPEPRMQconCATUGT2B15allele-specific protein expressionparallel reaction monitoringquantitative concatamer

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Area of Science:

  • Proteomics
  • Genetics
  • Molecular Biology

Background:

  • Allele-specific expression (ASE) analysis identifies cis-regulatory genetic variants.
  • Understanding post-transcriptional regulation is crucial for deciphering gene expression variability.

Purpose of the Study:

  • To develop and validate a novel targeted proteomics method for allele-specific protein expression (ASPE) quantification.
  • To investigate cis-regulatory variants influencing UGT2B15 protein expression in human livers.

Main Methods:

  • Utilized scheduled parallel reaction monitoring (PRM) for targeted proteomics.
  • Employed a heavy stable isotope-labeled quantitative concatamer (QconCAT) internal standard.
  • Applied the method to quantify ASPE of UGT2B15 using the Y85D variant (rs1902023).

Main Results:

  • Demonstrated accurate ASPE measurement of UGT2B15 in human liver samples.
  • Observed significant variability in allele ratios (0.60–1.46) among heterozygotes, indicating cis-regulatory variants.
  • Found no significant correlation between ASPE and mRNA ASE, suggesting distinct regulatory mechanisms.

Conclusions:

  • The developed ASPE method is a powerful tool for identifying cis-genetic variants affecting post-transcriptional regulation.
  • Highlights the importance of studying post-transcriptional regulatory mechanisms, which are often overlooked.
  • Provides insights into the differential regulation of transcription and translation by cis-acting variants.