A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig

Abstract

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.

A genome scan for selection signatures comparing farmed Atlantic salmon with two wild populations: Testing colocalization among outlier markers, candidate genes, and quantitative trait loci for production traits

“…Comparison of the genomes of domesticated species to their wild founder populations can help identify the genes underlying differentially selected traits, thereby advancing a fundamental goal of evolutionary biology (Stinchcombe & Hoekstra, 2008). Population genomics approaches have been used to support the hypothesis of artificial selection by humans over the past millennium causing allele frequency changes at major loci that determine cob size in maize (Vigouroux et al., 2002), muscle growth in pigs (Van Laere et al., 2003), and coat color in domestic mammals (Cieslak, Reissmann, Hofreiter, & Ludwig, 2011). Motivation behind genome scans for selection signatures lies in the possibility of finding DNA markers associated with traits of economic interest that can be used for marker‐assisted selection (López, Neira, & Yáñez, 2015; Yáñez, Houston, & Newman, 2014).…”

The Asp298Asn missense mutation in the porcine melanocortin-4 receptor (MC4R) gene can be used to affect growth and carcass traits without an effect on meat quality

“…With the advent of molecular genetic tools, selection may be further improved based on mutations in candidate genes or quantitative trait loci (QTL), e.g. the IGF-2 mutation in pigs affecting the percentage lean meat (Van Laere et al, 2003). However, improvement of performance traits may be associated with undesirable effects on meat quality, as has been clearly evidenced in the case of the RYR1 and the RN mutation (De Smet et al, 1995;Sellier, 1998;Hamilton et al, 2000).…”

Molecular cloning and polymorphism of the porcine H2AFZ gene

“…For example, the regulatory mutation in IGF2 gene, which causes a major QTL effect on muscle growth in the pig, is a single nucleotide polymorphism (G3072A) in intron 3 (Van Laere et al, 2003). However, before the polymorphism can be used for marker-assisted selection in genetic improvement of pigs, further evaluation and confirmation studies in more pig populations, with large sample sizes, are necessary.…”