title: Towards the molecular understanding of the polar overdominance phenomenon associated with the callipyge phenotype in sheep.
abstract: Most medically or agronomically important phenotypes are "complex" inherited traits. They are influenced by genes but not transmitted according to Mendel's laws. Recently, Steve Henikoff wrote: "The nature of quantitative-trait variation is one of the last unexplored frontiers in genetics, awaiting the future and definitive identification of complex trait determinants, wether they be genetic or epigenetic" (Nature Genetics, 2003). The callipyge phenotype is a muscular hypertrophy in sheep that is characterized by a complex inheritance pattern referred to as polar overdominance: only heterozygous individuals having received the CLPG mutation from their sire exhibit the phenotype. We have spent the last ten years attempting to dissect the molecular basis of this unique phenomenon. These studies have lead to a working model including: (i) DLKI, a paternally expressed growth promoter, (ii) a maternally expressed DLK1 trans-acting repressor that is likely to be a non-coding RNA, and (iii) the CLPG mutation inactivating a silencer element controlling both the expression of DLK1 and its trans-acting repressor in skeletal muscle. This research is not only of fundamental interest, but may as well lead to a better understanding and hence control of "complex" diseases exhibiting "parent-of-origin" effects.
authors: Faculté de Medecine Vétérinaire, Département des Productions Animales, ULg.
authors: C
authors: C
authors: Charlier
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D014644:Genetic Variation; D009154:Mutation; D010641:Phenotype; D040641:Quantitative Trait Loci; D012756:Sheep / Q000235:genetics*