A Missense Mutation in PPARD Causes a Major QTL Effect on Ear Size in Pigs

Abstract

Chinese Erhualian is the most prolific pig breed in the world. The breed exhibits exceptionally large and floppy ears. To identify genes underlying this typical feature, we previously performed a genome scan in a large scale White Duroc × Erhualian cross and mapped a major QTL for ear size to a 2-cM region on chromosome 7. We herein performed an identical-by-descent analysis that defined the QTL within a 750-kb region. Historically, the large-ear feature has been selected for the ancient sacrificial culture in Erhualian pigs. By using a selective sweep analysis, we then refined the critical region to a 630-kb interval containing 9 annotated genes. Four of the 9 genes are expressed in ear tissues of piglets. Of the 4 genes, PPARD stood out as the strongest candidate gene for its established role in skin homeostasis, cartilage development, and fat metabolism. No differential expression of PPARD was found in ear tissues at different growth stages between large-eared Erhualian and small-eared Duroc pigs. We further screened coding sequence variants in the PPARD gene and identified only one missense mutation (G32E) in a conserved functionally important domain. The protein-altering mutation showed perfect concordance (100%) with the QTL genotypes of all 19 founder animals segregating in the White Duroc × Erhualian cross and occurred at high frequencies exclusively in Chinese large-eared breeds. Moreover, the mutation is of functional significance; it mediates down-regulation of β-catenin and its target gene expression that is crucial for fat deposition in skin. Furthermore, the mutation was significantly associated with ear size across the experimental cross and diverse outbred populations. A worldwide survey of haplotype diversity revealed that the mutation event is of Chinese origin, likely after domestication. Taken together, we provide evidence that PPARD G32E is the variation underlying this major QTL.

Genome-Wide Scan Reveals LEMD3 and WIF1 on SSC5 as the Candidates for Porcine Ear Size

“…Considering a selective sweep region for ear size being reported on SSC7 in this breed [6], hence Erhualian was selected for case group with larger ear size in present study. Duroc (about 180 cm 2 ), Landrace (about 200 cm 2 ), and Large White (about 165 cm 2 ) were treated as control groups (Figure S2 in File S1).…”

Mining the pig genome to investigate the domestication process

“…Genome analyses have identified a number of regions and candidate loci that may be responsible, to some degree, for traits selected during and after domestication (Amaral et al, 2011;Mikawa et al, 2011;Ren et al, 2011;Rubin et al, 2012;Ai et al, 2013;Fan et al, 2013;Moutou et al, 2013;Wilkinson et al, 2013). In Table 2, genomic regions associated (directly or secondarily) with domestication traits are presented.…”

Mapping QTL for growth and muscling traits in three connected porcine F<sub>2</sub> crosses

“…The first candidate gene is called PPARD, which is involved in cartilage development as well as in fat metabolism. Ren et al (2011) described a missense mutation which is associated with ear size in Chinese pigs. The second one is the Bmp5 gene located at the short ear locus, which was investigated by Kingsley et al (1992).…”