The GGT 1 and IGFBP 5 genes are associated with fat deposition traits in the pig ( Brief Report )

In the earlier comparative linkage mapping of bone-related genes in the pig, the Gamma glutamyl transferase 1 (GGT1) gene was assigned between SWC6 and SWR84 on SSC14, and Insulin-like growth factor binding protein 5 (IGFBP5) gene was mapped between SW120 and SW936 on SSC15 (ONTERU et al. 2008). QTL related to average backfat and 10th rib backfat traits had been reported around these regions (http://www.animalgenome.org/cgi-bin/QTLdb, ROHRER et al. 1998, DE KONING et al. 2001, MALEK et al. 2001). Both genes did not have association with any of body conformation, feet and leg structure traits (FAN et al. 2009), but it is worth exploring whether they are associated with fatness. Here we carried out association analyses of the identified SNPs from the genes in two pig populations and investigated the possible effect of them on fat deposition traits.


Background
In the earlier comparative linkage mapping of bone-related genes in the pig, the Gamma glutamyl transferase 1 (GGT1) gene was assigned between SWC6 and SWR84 on SSC14, and Insulin-like growth factor binding protein 5 (IGFBP5) gene was mapped between SW120 and SW936 on SSC15 (ONTERU et al. 2008).QTL related to average backfat and 10th rib backfat traits had been reported around these regions (http://www.animalgenome.org/cgi-bin/QTLdb,ROHRER et al. 1998, DE KONING et al. 2001, MALEK et al. 2001).Both genes did not have association with any of body conformation, feet and leg structure traits (FAN et al. 2009), but it is worth exploring whether they are associated with fatness.Here we carried out association analyses of the identified SNPs from the genes in two pig populations and investigated the possible effect of them on fat deposition traits.

Procedures
The SNPs c.884-228C>G (dbSNP acc.no.ss86352433) within GGT1 intron 11 and c.567+79A>C (dbSNP acc.no.ss86352413) within IGFBP5 intron 2 were detected in the previous study (FAN et al. 2009).SNP genotyping was implemented in two different pig populations using a high throughout MassARRAY system (Sequenom Inc, San Diego, CA, USA).Population A consisted of 2 066 commercial sows from Newsham Choice Genetics.The 10th rib and last rib backfat thickness were measured using an ultrasonic imaging approach with a Pie Medical 200 (Classic Medical Supply Inc., Tequesta, FL, USA).The association analyses between the SNPs and traits were performed using the MIXED procedure (SAS 9.0, SAS Institute, Cary, NC, USA), with a statistical model treating genetic line, measurement date and marker genotype as fixed effects, sire as a random effect and body weight as a covariate.Population B, the ISU Berkshire × Yorkshire (B×Y) pig resource family is comprised of 11 F0, 35 F1 and 515 F2 animals.The measurements of four backfat traits including average backfat, backfat at 10th rib, lumbar and last rib points were described by MALEK et al. (2001).The association analyses were performed using the MIXED model procedure, including sex, slaughter date and marker genotypes as fixed effects, dam (litter) as a random effect and body weight as a covariate.

Results
The analyzed SNPs showed a high level of polymorphism in both pig populations and had minor allele frequency greater than 0.05.In population A, GGT1 c.884-228C>G was significantly (P<0.05)associated with 10th rib backfat while it was not associated with last rib backfat (Table 1).In the B×Y pig family, c.884-228C>G was very highly significantly (P<0.001)associated with all of the four different backfat traits.The allele C was favorably associated with leanness in population A and similarly it was associated with less fatness in the B×Y pig family.IGFBP5 c.567+79A>C was significantly associated (P<0.05) with last rib backfat and suggestively significantly associated (P<0.1) with 10th rib backfat in population A. In the B×Y pig family, c.567+79A>C was very highly significantly (P<0.001)associated with 10th rib backfat and significantly (P<0.05)associated with average backfat, but it was not associated with both lumbar backfat and last rib backfat traits.The allele A was desirable as it was associated with leanness in both populations.GGT1 is one of potential markers for bone resorption and acts as a pathological bone resorbing factor by stimulating RANK ligand (ASABA et al. 2006).Most recently, a genomewide association study in humans revealed that intronic SNPs within the GGT1 and HNF1A genes were associated with gamma-glutamyl transferase level, which is usually used as indicator of biliary or cholestatic diseases and heavy alcohol consumption (YUAN et al. 2008).The genes GGT1 and HNF1A are located on human chromosomes 22q 11.23 and 12q 24.31 , respectively, but their corresponding porcine genes were mapped between SWC6 and SWR84 on SSC14.The HNF1A (also known as TCF1) gene was associated with the type III form of maturity-onset diabetes of the young people (MODY3) in humans (ELLARD 2000).It is speculated that either the GGT1 gene has an independent effect on adipose tissue development and deposition, or the possible linkage disequilibrium between these two genes resulted in association of the GGT1 gene with backfat.
IGFBP5 is one of the members of the insulin-like growth factor binding proteins (IGFBPs) family, and it is primarily expressed in bone tissue and helps to potentiate the action of IGFI on smooth muscle cells, fibroblasts or osteoblasts.The IGFBP5 gene might be involved in intramuscular fat development in the cattle (WANG et al. 2009), and was also associated with serum adiponectin concentrations in humans, which play a crucial role in the modulation of glucose metabolism in insulin-sensitive tissues such as adipose tissue (KALLIO et al. 2009).The results from this study suggested that the IGFBP5 gene is associated with fat deposition in pigs.Further work on causative mutation discovery and function analysis of the GGT1 and IGFBP5 genes are needed before they can be recommended for marker assisted selection.

Table 1
Association of the SNPs within GGT1 and IGFBP5 genes with backfat traits in two pig populations, respectively Assoziation der SNPs der Gene GGT1 und IGFBP5 mit der Rückenfettdicke in zwei Schweinepopulationen