Comparative sequence analysis of the Insulin-IGF2 region harbouring a major QTL for muscle development in the pig

We and others have identified a paternally expressed Quantitative Trait Locus (QTL) primarily affecting muscle development at the distal tip of pig chromosome 2p. IGF2 (Insulin-like Growth Factor 2) was identified as the major candidate gene due to its perfect co-localisation with the QTL, its paternal imprinting, and its important role in prenatal development in mammals. This QTL is segregating in our Wild Boar/Large White intercross and previous studies did not reveal any sequence difference in the IGF2 coding sequence. Thus, we assume that the QTL may be due to one or more regulatory mutations. We have now determined 32 kb contiguous genomic sequence containing the Insulin-IGF2 region. This region contains a very high GC content, many CpG islands and very few interspersed repeats. A comparative sequence analysis with the homologous region in humans and mouse revealed that all coding sequences are well conserved between species but also that a large proportion of the non-coding sequence in this region is surprisingly well conserved between species. The results will facilitate the further characterization of this important QTL in the pig and we are currently doing comparative sequence analysis of chromosomes with known QTL status in the search for causative mutation(s).