OpenSSL SSL_connect: Connection reset by peer in connection to v2.sherpa.ac.uk:443 PuSH - Publication Server of Helmholtz Zentrum München: A systems biology approach using metabolomic data reveals genes and pathways interacting to modulate divergent growth in cattle.

PuSH - Publication Server of Helmholtz Zentrum München

Widmann, P.* ; Reverter, A.* ; Fortes, M.R.* ; Weikard, R.* ; Suhre, K. ; Hammon, H.* ; Albrecht, E.* ; Kuehn, C.*

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

BMC Genomics 14:798 (2013)
Publ. Version/Full Text Volltext DOI PMC
Open Access Gold
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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.  
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cattle ; Segfam ; Systems Biology ; Metabolomics ; Genome-wide Association Study ; Divergent Growth ; Puberty; Genome-wide Association; Neuroendocrine Regulation; Chromosome Condensation; Sequence Variants; Nitric Oxide; Body-weight; Muscle Mass; Bos-taurus; Networks; Complex
ISSN (print) / ISBN 1471-2164
e-ISSN 1471-2164
Journal BMC Genomics
Quellenangaben Volume: 14, Issue: 1, Pages: , Article Number: 798 Supplement: ,
Publisher BioMed Central
Non-patent literature Publications
Reviewing status Peer reviewed