A systems biology approach using metabolomic data reveals genes and pathways interacting to modulate divergent growth in cattle

Widmann, Philipp, Reverter, Antonio, Fortes, Marina R. S., Weikard, Rosemarie, Suhre, Karsten, Hammon, Harald, Albrecht, Elke and Kuehn, Christa (2013) A systems biology approach using metabolomic data reveals genes and pathways interacting to modulate divergent growth in cattle. BMC Genomics, 14 1: 798.1-798.17. doi:10.1186/1471-2164-14-798


Author Widmann, Philipp
Reverter, Antonio
Fortes, Marina R. S.
Weikard, Rosemarie
Suhre, Karsten
Hammon, Harald
Albrecht, Elke
Kuehn, Christa
Title A systems biology approach using metabolomic data reveals genes and pathways interacting to modulate divergent growth in cattle
Journal name BMC Genomics   Check publisher's open access policy
ISSN 1471-2164
Publication date 2013-11-18
Sub-type Article (original research)
DOI 10.1186/1471-2164-14-798
Open Access Status DOI
Volume 14
Issue 1
Start page 798.1
End page 798.17
Total pages 17
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Subject 1305 Biotechnology
1311 Genetics
Formatted abstract
Background: Systems biology enables the identification of gene networks that modulate complex traits. Comprehensive metabolomic analyses provide innovative phenotypes that are intermediate between the initiator of genetic variability, the genome, and raw phenotypes that are influenced by a large number of environmental effects. The present study combines two concepts, systems biology and metabolic analyses, in an approach without prior functional hypothesis in order to dissect genes and molecular pathways that modulate differential growth at the onset of puberty in male cattle. Furthermore, this integrative strategy was applied to specifically explore distinctive gene interactions of non-SMC condensin I complex, subunit G (NCAPG) and myostatin (GDF8), known modulators of pre- and postnatal growth that are only partially understood for their molecular pathways affecting differential body weight.

Results: Our study successfully established gene networks and interacting partners affecting growth at the onset of puberty in cattle. We demonstrated the biological relevance of the created networks by comparison to randomly created networks. Our data showed that GnRH (Gonadotropin-releasing hormone) signaling is associated with divergent growth at the onset of puberty and revealed two highly connected hubs, BTC and DGKH, within the network. Both genes are known to directly interact with the GnRH signaling pathway. Furthermore, a gene interaction network for NCAPG containing 14 densely connected genes revealed novel information concerning the functional role of NCAPG in divergent growth.

Conclusions: Merging both concepts, systems biology and metabolomic analyses, successfully yielded new insights into gene networks and interacting partners affecting growth at the onset of puberty in cattle. Genetic modulation in GnRH signaling was identified as key modifier of differential cattle growth at the onset of puberty. In addition, the benefit of our innovative concept without prior functional hypothesis was demonstrated by data suggesting that NCAPG might contribute to vascular smooth muscle contraction by indirect effects on the NO pathway via modulation of arginine metabolism. Our study shows for the first time in cattle that integration of genetic, physiological and metabolomics data in a systems biology approach will enable (or contribute to) an improved understanding of metabolic and gene networks and genotype-phenotype relationships. 
Keyword Cattle
Divergent growth
Genome-wide association study
Metabolomics
Puberty
SEGFAM
Systems biology
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Alliance for Agriculture and Food Innovation
Official 2014 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 17 times in Scopus Article | Citations
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Created: Tue, 10 Dec 2013, 10:46:40 EST by System User on behalf of Qld Alliance for Agriculture and Food Innovation