Obesity represents a major global public health problem that increases the risk for cardiovascular or metabolic disease. The pigs represent an exceptional biomedical model related to energy metabolism and obesity in humans. To pinpoint causal genetic factors for a common form of obesity, we conducted local genomic de novo sequencing, 18.2 Mb, of a porcine QTL region affecting fatness traits, and carried out SNP association studies for backfat thickness and intramuscular fat content in pigs. In order to relate the association studies in pigs to human obesity, we performed a targeted genome wide association study for subcutaneous fat thickness in a cohort population of 8,842 Korean individuals. These combined association studies in human and pig revealed a significant SNP located in a gene family with sequence similarity 73, member A (FAM73A) associated with subscapular skin-fold thickness in humans (rs4121165, GC-corrected p-value  = 0.0000175) and with backfat thickness in pigs (ASGA0029495, p-value  = 0.000031). Our combined association studies also suggest that eight neuronal genes are responsible for subcutaneous fat thickness: NEGR1, SLC44A5, PDE4B, LPHN2, ELTD1, ST6GALNAC3, ST6GALNAC5, and TTLL7. These results provide strong support for a major involvement of the CNS in the genetic predisposition to a common form of obesity.

In order to analyze the genetic diversity and phylogenetic status of the Korean Chikso breed, we determined sequences of mtDNA cytochrome b (cyt b) gene and performed phylogenetic analysis using 239 individuals from 5 Chikso populations. Five non-synonymous mutations of a total of 15 polymorphic sites were identified among 239 cyt b coding sequences. Thirteen haplotypes were defined, and haplotype diversity was 0.4709 ranging from 0.2577 to 0.6114. Thirty-five haplotypes (C1–C35) were classified among 9 Asia and 3 European breeds. C2 was a major haplotype that contained 206 sequences (64.6%) from all breeds used. C3–C13 haplotypes were Chikso-specific haplotypes. C1 and C2 haplotypes contained 80.5% of cyt b sequences of Hanwoo, Yanbian, Zaosheng and JB breeds. In phylogenetic analyses, the Chikso breed was contained into B. taurus lineage and was genetically more closely related to two Chinese breeds than to Korean brown cattle, Hanwoo. These results suggest that Chikso and Hanwoo have a genetic difference based on the mtDNA cyt b gene as well as their coat color, sufficient for classification as a separate breed.

The porcine adenylate kinase 3-like 1 (AK3L1) gene is considered as a potential candidate gene among the encoded isoforms of adenylate kinase for meat quality based on the functional role of the AK3L1 gene in energy metabolism via high-energy phosphoryl transfer reaction. The genomic position of the AK3L1 gene is located in the QTL region, which codes for traits of meat quality. We characterized the genomic structure of the porcine AK3L1 gene and found polymorphisms in the 5' regulatory region. Typical transcription factor binding sites, such as the TATA box and initiator sequence, were not found. However, the AK3L1 gene had two different transcription start points with different transcripts from Exon 1a and 1b isoforms within the high G+C content region without changing the translation initiation site. The SNPs around two alternative transcription start points in the porcine AK3L1 gene were significantly associated with the following traits of meat quality: back fat thickness (SNP1, P < 0.01), IMF (SNP5, P < 0.06), muscle pH (SNP4, P < 0.05), meat color (SNP1, P < 0.03), and drip loss (SNP1, 2, 4, and 5, P < 0.04). We suggest that SNPs of the AK3L1 gene can induce variation in meat formation and may be potential markers for the quality of pig meat.The first two authors, HYL and JMK, contributed equally to this work.