Polar overdominant inheritance of a DLK1 polymorphism is associated with growth and fatness in pigs

Abstract

The polar overdominance model of inheritance was proposed to explain the non-Mendelian expression of callipyge muscular hypertrophy in sheep. The callipyge locus (CLPG) maps to the distal portion of ovine Chromosome 18 within the DLK1-GTL2 region and corresponds to human Chromosome 14q32, where uniparental disomy (UPD) of the region is associated with multiple congenital anomalies, including growth retardation and obesity. We investigated the porcine DLK1-GTL2 region in a cross of two pig breeds to determine if the callipyge polar overdominance is present in another species. Analyses of the parental origin of DLK1 polymorphism in the F2 offspring found that paternal inheritance of DLK1 allele 2 and maternal inheritance of the allele 1 was significantly associated with decreased fat deposition and increased lean muscle mass, while the opposite parental inheritance of these alleles was associated with slower prenatal and postnatal growth. These results suggest that the polar overdominance mode of inheritance is present in the pig chromosomal region that is homologous to the CLPG locus in sheep. Further study in pigs can provide important insights into understanding the molecular regulation of imprinted genes that are associated with human UPD14 and sheep callipyge phenotypes.

Preferential reciprocal transfer of paternal/maternal DLK1 alleles to obese children: first evidence of polar overdominance in humans

“…Animals having inherited one allele of this polymorphism from the father and the other allele from the mother were less fat and had increased lean body mass compared with all other genotypes. 12 In our study in humans, a synonymous polymorphism (rs1802710) in the fifth exon of DLK1, only 93 bp 5 0 of the relevant polymorphism in the orthologous pig sequence, was associated with extreme obesity. This was revealed by a hypothesis-driven analysis assuming an inheritance pattern compatible with polar overdominance, which was originally reported in sheep.…”

“…Again, sequencing of pig DNA fragments homologous to the Dlk1-Gtl2 region did not reveal additional polymorphisms. 12 This suggests that in both pig and human the exon 5 polymorphisms are either in LD with a causative mutation most likely outside of the analysed region or that the altered DNA sequences are causative themselves.…”

“…11 Evidence of polar overdominance has also been reported in pigs. 12 Analysis of the parental origin of a silent polymorphism in Dlk1 revealed that paternal inheritance of one allele and maternal inheritance of the other allele in F2 offspring of two intercrossed lines is associated with decreased fatness and increased lean body mass.…”

A catalogue of validated single nucleotide polymorphisms in bovine orthologs of mammalian imprinted genes and associations with beef production traits

“…Previous genome scans for production trait studies using multi-generational livestock resource populations have incorporated the effect of imprinting and monoallelic expression Rattink et al, 2000;Nezer et al, 2002;Holl et al, 2004;Kim et al, 2004b;Karlskov-Mortensen et al, 2006;Markljung et al, 2008;Duthie et al, 2009). In this study, however, it was not possible to include parent-of-origin effects in our statistical analyses as the Limousin population used was not multigenerational.…”

Polymorphisms in the delta-like 2 homolog gene and their association with growth and meat-quality traits in Qinchuan cattle

“…The NOTCH signaling pathway plays a highly important role in cell differentiation, proliferation, and developmental processes (Demarest et al, 2008), and anomalous NOTCH signaling can lead to tumorigenesis (Wu et al, 2007;Leong and Gao, 2008;Maliekal et al, 2008). It has been proposed that in F2 offspring obtained in breeding, different genotypes of DLK1 gene are associated with fat deposition and lean muscle mass (Kim et al, 2004). DLK1 may reduce intramuscular fat and inhibit adipogenesis, and the muscular hypertrophies of callipyge sheep, while the DLK1 gene is highly expressed in Longissimus dorsi or Supraspinatus as determined by immunohistochemistry (Davis et al, 2004).…”