Protein Quantitative Trait Loci Identify Novel Candidates Modulating Cellular Response to Chemotherapy
The central dogma of biology explains that DNA is transcribed to mRNA that is further translated into protein. Many genome-wide studies have implicated genetic variation that influences gene expression and that ultimately affect downstream complex traits including response to drugs. However, because of technical limitations, few studies have evaluated the contribution of genetic variation on protein expression and ensuing effects on downstream phenotypes. To overcome this challenge, we used a novel technology to simultaneously measure the baseline expression of 441 proteins in lymphoblastoid cell lines and compared them with publicly available genetic data. To further illustrate the utility of this approach, we compared protein-level measurements with chemotherapeutic induced apoptosis and cell-growth inhibition data. This study demonstrates the importance of using protein information to understand the functional consequences of genetic variants identified in genome-wide association studies. This protein data set will also have broad utility for understanding the relationship between other genome-wide studies of complex traits.
Vyšlo v časopise:
Protein Quantitative Trait Loci Identify Novel Candidates Modulating Cellular Response to Chemotherapy. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004192
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1004192
Souhrn
The central dogma of biology explains that DNA is transcribed to mRNA that is further translated into protein. Many genome-wide studies have implicated genetic variation that influences gene expression and that ultimately affect downstream complex traits including response to drugs. However, because of technical limitations, few studies have evaluated the contribution of genetic variation on protein expression and ensuing effects on downstream phenotypes. To overcome this challenge, we used a novel technology to simultaneously measure the baseline expression of 441 proteins in lymphoblastoid cell lines and compared them with publicly available genetic data. To further illustrate the utility of this approach, we compared protein-level measurements with chemotherapeutic induced apoptosis and cell-growth inhibition data. This study demonstrates the importance of using protein information to understand the functional consequences of genetic variants identified in genome-wide association studies. This protein data set will also have broad utility for understanding the relationship between other genome-wide studies of complex traits.
Zdroje
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Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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