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Combining plasma screening with genetic screening better identifies diagnostic and therapeutic targets

Date:
February 8, 2013
Source:
Genetics Society of America
Summary:
New research shows that marrying genome-wide and proteome-wide screening helps determine susceptibility in a wide variety of diseases.
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For the first time, scientists have combined genomic and proteomic analysis of blood plasma to enhance identification of genetically regulated protein traits. This could be applied to any large association study of civilization diseases where blood plasma has been collected, vastly improving a clinician's ability to identify disease susceptibility in individuals and populations.

"We hope that combining genome-wide with proteome-wide screening of blood plasma will aid in the identification of molecular disease mechanisms," said Daniel Teupser, M.D., a researcher involved in the work from the Institute of Laboratory Medicine at Ludwig-Maximilians-University, in Munich, Germany. "The methodology is applicable to many frequent diseases such as diabetes, cardiovascular disease or cancer and might accelerate identification of novel diagnostic and therapeutic targets."

To make this advance, Teupser and colleagues analyzed 455 plasma samples from the offspring of two different inbred mouse strains using mass spectrometry. This allows researchers to distinguish proteins based on differences in their molecular weight. The resulting protein phenotypes of all 455 F2 mice were associated with 177 genetic markers evenly distributed over the mouse genome. This led to the identification of genetically regulated plasma proteins. The strongest two associations were with the genes encoding hemoglobin and apolipoprotein 2. The responsible genetic variants were identified in additional functional experiments.

Mass spectrometry has already been adapted for clinical applications, and plasma is often the target because of it easy accessibility. Since plasma comes in contact with most tissues, it often mirrors metabolism and disease. This study pioneers a promising approach to identify novel disease-associated proteins, which could provide novel diagnostic or therapeutic targets of disease.   "Gene variants are now easy to identify, so what's become limiting is the traits -- the phenotype -- to link to those variants. This study goes a long way to opening up that bottleneck. The high-throughput screening the authors describe holds tremendous promise for finding diagnostic markers and therapeutic targets of disease," said Mark Johnston, Editor-in-Chief of the journal GENETICS.


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The above post is reprinted from materials provided by Genetics Society of America. Note: Materials may be edited for content and length.


Journal Reference:

  1. L. M. Holdt, A. von Delft, A. Nicolaou, S. Baumann, M. Kostrzewa, J. Thiery, D. Teupser. Quantitative Trait Loci Mapping of the Mouse Plasma Proteome (pQTL). Genetics, 2012; 193 (2): 601 DOI: 10.1534/genetics.112.143354

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Genetics Society of America. "Combining plasma screening with genetic screening better identifies diagnostic and therapeutic targets." ScienceDaily. ScienceDaily, 8 February 2013. <www.sciencedaily.com/releases/2013/02/130208105301.htm>.
Genetics Society of America. (2013, February 8). Combining plasma screening with genetic screening better identifies diagnostic and therapeutic targets. ScienceDaily. Retrieved July 28, 2015 from www.sciencedaily.com/releases/2013/02/130208105301.htm
Genetics Society of America. "Combining plasma screening with genetic screening better identifies diagnostic and therapeutic targets." ScienceDaily. www.sciencedaily.com/releases/2013/02/130208105301.htm (accessed July 28, 2015).

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