Genome-wide association studies and meta-analysis reveal novel quantitative trait loci and pleiotropic loci for swine head-related traits 1,2

The pig is an important domestic animal that provides a larger amount of meat and serves as a biomedical animal model for human. Head and facial features are closely linked to identity recognition in mammal communication. To uncover the genetic architecture of swine head and facial features, we constructed 5 experimental pig populations and accurately measured 10 traits related to head and facial features, for which genome-wide association studies and meta-analysis were later carried out. As a result, we identified a total of 24 loci harboring 437 SNP on 8 swine chromosomes (SSC) that surpassed suggestively significant levels, of which 17 loci on 6 chromosomes exceeded the 5% genome-wide significance thresholds. To our knowledge, this is the first report of QTL for the distance from the low corner of the eye to the snout end (DES) and to the mouth corner (DEM), the size of extra mouth cleft (EMC), lip thickness, head length, and tongue weight and length in pigs. Notably, 3 pleiotropic loci were detected, including the loci at 298.1 Mb on SSC1 for head length and DES, at about 80.0 Mb on SSC4 for head weight, tongue weight and length, and at 34.8 Mb on SSC7 for head weight, EMC, and lip thickness. Several positional candidate genes at the identified loci might play roles in craniofacial development or have been implicated in syndromes affecting human head and facial features, including glutamate metabotropic receptor 4 (GRM4), high mobility group AT-hook 1 (HMGA1), high mobility group AT-hook 2 (HMGA2), serum/glucocorticoid regulated kinase family member 3 (SGK3), pleiomorphic adenoma gene 1 (PLAG1), proto-oncogene serine/threonine-protein kinase mos (MOS) and DENN (differentially expressed in normal and neoplastic cells) domain containing 1A (DENND1A). These findings will contribute to further detection of the causal mutations underlying these QTL for head and facial features in pigs and provide insights into the genetic basis of head and facial characteristics in human or other mammals.