Quantitative detection of single amino acid polymorphisms by targeted proteomics.
Single-nucleotide polymorphisms (SNPs) are recognized as one kind of major genetic variants in population scale. However, polymorphisms at the proteome level in population scale remain elusive. In the present study, we named amino acid variances derived from SNPs within coding regions as single amino acid polymorphisms (SAPs) at the proteome level, and developed a pipeline of non-targeted and targeted proteomics to identify and quantify SAP peptides in human plasma. The absolute concentrations of three selected SAP-peptide pairs among 290 Asian individuals were measured by selected reaction monitoring (SRM) approach, and their associations with both obesity and diabetes were further analyzed. This work revealed that heterozygotes and homozygotes with various SAPs in a population could have different associations with particular traits. In addition, the SRM approach allows us for the first time to separately measure the absolute concentration of each SAP peptide in the heterozygotes, which also shows different associations with particular traits.
Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Zhi-Duan
ZD
Su
Liang
L
Sun
Dan-Xia
DX
Yu
Rong-Xia
RX
Li
Huai-Xing
HX
Li
Zhi-Jie
ZJ
Yu
Quan-Hu
QH
Sheng
Xu
X
Lin
Rong
R
Zeng
Jia-Rui
JR
Wu
D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020543:Proteome / Q000032:analysis / Q000235:genetics; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry
D010455:Peptides; D020543:Proteome