A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig. Academic Article uri icon


  • Most traits and disorders have a multifactorial background indicating that they are controlled by environmental factors as well as an unknown number of quantitative trait loci (QTLs). The identification of mutations underlying QTLs is a challenge because each locus explains only a fraction of the phenotypic variation. A paternally expressed QTL affecting muscle growth, fat deposition and size of the heart in pigs maps to the IGF2 (insulin-like growth factor 2) region. Here we show that this QTL is caused by a nucleotide substitution in intron 3 of IGF2. The mutation occurs in an evolutionarily conserved CpG island that is hypomethylated in skeletal muscle. The mutation abrogates in vitro interaction with a nuclear factor, probably a repressor, and pigs inheriting the mutation from their sire have a threefold increase in IGF2 messenger RNA expression in postnatal muscle. Our study establishes a causal relationship between a single-base-pair substitution in a non-coding region and a QTL effect. The result supports the long-held view that regulatory mutations are important for controlling phenotypic variation.

published proceedings

  • Nature

altmetric score

  • 13.35

author list (cited authors)

  • Van Laere, A., Nguyen, M., Braunschweig, M., Nezer, C., Collette, C., Moreau, L., ... Andersson, L.

citation count

  • 679

complete list of authors

  • Van Laere, Anne-Sophie||Nguyen, Minh||Braunschweig, Martin||Nezer, Carine||Collette, Catherine||Moreau, Laurence||Archibald, Alan L||Haley, Chris S||Buys, Nadine||Tally, Michael||Andersson, Göran||Georges, Michel||Andersson, Leif

publication date

  • October 2003

published in