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

Abstract

BackgroundSystems 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.ResultsOur 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.ConclusionsMerging 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.

Multimarker and rare variants genomewide association studies for bone weight in Simmental cattle

“…A genomewide scan for selection signatures in ten cattle breeds revealed that MAP2K6 is associated with carcass weight, back fat and marbling in Korean beef cattle (Rothammer, Seichter, Förster, & Medugorac, ). Furthermore, MAP2K6 participates in the gonadotropin signalling pathway, which has been identified to be associated with divergent growth traits according to a multiomics analysis in an F 2 Charolais × Holstein population (Widmann et al., ). Regarding pigs, MAP2K6 has been associated with growth traits in the purebred Yorkshire strain (Meng et al., ) and with foot and leg structural soundness traits in domestic pigs in general (Meng et al., ).…”

Genome-wide detection of copy-number variations in local cattle breeds

“…Other putative candidate genes included SMAD9, which encodes a protein with a potentially important role in follicular initiation and development (Xu et al 2015), GRIK2, which encodes a protein that plays important physiological roles in maturation and puberty (Widmann et al 2013), LRBA, which encodes a protein related to reproductive traits (Taye et al 2017), H19, which encodes a protein associated with embryogenesis and fetal growth in livestock species (Zaitoun and Khatib 2006) and IGF2, which encodes a protein considered to regulate the postnatal growth and differentiation of the mammary gland (Bagnicka et al 2010). The protein encoded byLSP1 has a negative regulatory role in leukocyte recruitment to sites of inflammation and in resistance/susceptibility to intestinal nematodes (Hou et al 2012a).…”

Reducing the interval of a growth QTL on chromosome 4 in laying hens

“…Furthermore, the NCAPG gene has been shown to influence vascular smooth muscle contraction through indirect effects on arginine‐NO metabolism (Widmann et al . ). Therefore, NCAPG could influence growth through regulation of arginine metabolism.…”