Combining plasma screening methods better identifies diagnostic and therapeutic targets

Public release date: 8-Feb-2013
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Contact: Phyllis Edelman
pedelman@genetics-gsa.org
301-634-7302
Genetics Society of America

Research published in the journal Genetics shows that marrying genome-wide and proteome-wide screening helps determine susceptibility in a wide variety of diseases

BETHESDA, MD February 8, 2013 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. This advance is published in the February 2013 issue of the journal Genetics.

"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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CITATION: Holdt, Lesca M., Annette von Delft, Alexandros Nicolaou, Sven Baumann, Markus Kostrzewa, Joachim Thiery, and Daniel Teupser
Quantitative Trait Loci Mapping of the Mouse Plasma Proteome (pQTL)
Genetics February 2013 193:601-608.

FUNDING: This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft (DFG, TE 342/7-1) to Dr. Daniel Teupser.

ABOUT GENETICS: Since 1916, Genetics has covered high quality, original research on a range of topics bearing on inheritance, including population and evolutionary genetics, complex traits, developmental and behavioral genetics, cellular genetics, gene expression, genome integrity and transmission, and genome and systems biology. Genetics, a peer-reviewed, peer-edited journal of the Genetics Society of America is one of the world's most cited journals in genetics and heredity.

ABOUT GSA: Founded in 1931, the Genetics Society of America (GSA) is the professional membership organization for scientific researchers, educators, bioengineers, bioinformaticians and others interested in the field of genetics. Its nearly 5,000 members work to advance knowledge in the basic mechanisms of inheritance, from the molecular to the population level. The GSA is dedicated to promoting research in genetics and to facilitating communication among geneticists worldwide through its conferences, including the biennial conference on Model Organisms to Human Biology, an interdisciplinary meeting on current and cutting edge topics in genetics research, as well as annual and biennial meetings that focus on the genetics of particular organisms, including C. elegans, Drosophila, fungi, mice, yeast, and zebrafish. GSA publishes Genetics, a leading journal in the field and an online, open-access journal, G3: Genes|Genomes|Genetics. For more information about GSA, please visit www.genetics-gsa.org. Also follow GSA on Facebook at facebook.com/GeneticsGSA and on Twitter @GeneticsGSA.

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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Public release date: 8-Feb-2013
[ | E-mail | Share ]

Contact: Phyllis Edelman
pedelman@genetics-gsa.org
301-634-7302
Genetics Society of America

Research published in the journal Genetics shows that marrying genome-wide and proteome-wide screening helps determine susceptibility in a wide variety of diseases

BETHESDA, MD February 8, 2013 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. This advance is published in the February 2013 issue of the journal Genetics.

"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.

###

CITATION: Holdt, Lesca M., Annette von Delft, Alexandros Nicolaou, Sven Baumann, Markus Kostrzewa, Joachim Thiery, and Daniel Teupser
Quantitative Trait Loci Mapping of the Mouse Plasma Proteome (pQTL)
Genetics February 2013 193:601-608.

FUNDING: This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft (DFG, TE 342/7-1) to Dr. Daniel Teupser.

ABOUT GENETICS: Since 1916, Genetics has covered high quality, original research on a range of topics bearing on inheritance, including population and evolutionary genetics, complex traits, developmental and behavioral genetics, cellular genetics, gene expression, genome integrity and transmission, and genome and systems biology. Genetics, a peer-reviewed, peer-edited journal of the Genetics Society of America is one of the world's most cited journals in genetics and heredity.

ABOUT GSA: Founded in 1931, the Genetics Society of America (GSA) is the professional membership organization for scientific researchers, educators, bioengineers, bioinformaticians and others interested in the field of genetics. Its nearly 5,000 members work to advance knowledge in the basic mechanisms of inheritance, from the molecular to the population level. The GSA is dedicated to promoting research in genetics and to facilitating communication among geneticists worldwide through its conferences, including the biennial conference on Model Organisms to Human Biology, an interdisciplinary meeting on current and cutting edge topics in genetics research, as well as annual and biennial meetings that focus on the genetics of particular organisms, including C. elegans, Drosophila, fungi, mice, yeast, and zebrafish. GSA publishes Genetics, a leading journal in the field and an online, open-access journal, G3: Genes|Genomes|Genetics. For more information about GSA, please visit www.genetics-gsa.org. Also follow GSA on Facebook at facebook.com/GeneticsGSA and on Twitter @GeneticsGSA.

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[ | E-mail | Share ]

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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Source: http://www.eurekalert.org/pub_releases/2013-02/gsoa-cp020613.php

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