Metabolomic profiles indicate distinct physiological pathways affected by two loci with major divergent effect on Bos taurus growth and lipid deposition

Rosemarie Weikard, Elisabeth Altmaier, Karsten Suhre, Klaus M. Weinberger, Harald M. Hammon, Elke Albrecht, Kouji Setoguchi, Akiko Takasuga, Christa Kühn

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Identifying trait-associated genetic variation offers new prospects to reveal novel physiological pathways modulating complex traits. Taking advantage of a unique animal model, we identified the I442M mutation in the non-SMC condensin I complex, subunit G (NCAPG) gene and the Q204X mutation in the growth differentiation factor 8 (GDF8) gene as substantial modulators of pre- and/or postnatal growth in cattle. In a combined metabolomic and genotype association approach, which is the first respective study in livestock, we surveyed the specific physiological background of the effects of both loci on body-mass gain and lipid deposition. Our data provided confirming evidence from two historically and geographically distant cattle populations that the onset of puberty is the key interval of divergent growth. The locus-specific metabolic patterns obtained from monitoring 201 plasma metabolites at puberty mirror the particular NCAPG I442M and GDF8 Q204X effects and represent biosignatures of divergent physiological pathways potentially modulating effects on proportional and disproportional growth, respectively. While the NCAPG I442M mutation affected the arginine metabolism, the 204X allele in the GDF8 gene predominantly raised the carnitine level and had concordant effects on glycerophosphatidylcholines and sphingomyelins. Our study provides a conclusive link between the well-described growth-regulating functions of arginine metabolism and the previously unknown specific physiological role of the NCAPG protein in mammalian metabolism. Owing to the confirmed effect of the NCAPG/LCORL locus on human height in genome-wide association studies, the results obtained for bovine NCAPG might add valuable, comparative information on the physiological background of genetically determined divergent mammalian growth.

Original languageEnglish
Pages (from-to)79-88
Number of pages10
JournalPhysiological Genomics
Volume42 A
Issue number2
DOIs
Publication statusPublished - Sep 2010
Externally publishedYes

Fingerprint

Metabolomics
Myostatin
Lipids
Growth
Puberty
Mutation
Arginine
Genes
Sphingomyelins
Carnitine
Genome-Wide Association Study
Livestock
Animal Models
Alleles
Genotype
Population
Proteins

Keywords

  • Arginine
  • Carnitine
  • Disproportional growth
  • Genetic association
  • Non-SMC condensin I complex, subunit G gene

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Metabolomic profiles indicate distinct physiological pathways affected by two loci with major divergent effect on Bos taurus growth and lipid deposition. / Weikard, Rosemarie; Altmaier, Elisabeth; Suhre, Karsten; Weinberger, Klaus M.; Hammon, Harald M.; Albrecht, Elke; Setoguchi, Kouji; Takasuga, Akiko; Kühn, Christa.

In: Physiological Genomics, Vol. 42 A, No. 2, 09.2010, p. 79-88.

Research output: Contribution to journalArticle

Weikard, Rosemarie ; Altmaier, Elisabeth ; Suhre, Karsten ; Weinberger, Klaus M. ; Hammon, Harald M. ; Albrecht, Elke ; Setoguchi, Kouji ; Takasuga, Akiko ; Kühn, Christa. / Metabolomic profiles indicate distinct physiological pathways affected by two loci with major divergent effect on Bos taurus growth and lipid deposition. In: Physiological Genomics. 2010 ; Vol. 42 A, No. 2. pp. 79-88.
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