Insulin resistance occurs early in the disease process, preceding the development of type 2 diabetes. Therefore, the identification of molecules that contribute to insulin resistance and leading up to type 2 diabetes is important to elucidate the molecular pathogenesis of the disease. To this end, we characterized gene expression profiles from insulin-sensitive tissues, including adipose tissue, skeletal muscle, and liver tissue of Zucker diabetic fatty (ZDF) rats, a well characterized type 2 diabetes animal model. Gene expression profiles from ZDF rats at 6 weeks (pre-diabetes), 12 weeks (diabetes), and 20 weeks (late-stage diabetes) were compared with age-and sex-matched Zucker lean control (ZLC) rats using 5000 cDNA chips. Differentially regulated genes demonstrating.1·3-fold change at age were identified and categorized through hierarchical clustering analysis. Our results showed that while expression of lipolytic genes was elevated in adipose tissue of diabetic ZDF rats at 12 weeks of age, expression of lipogenic genes was decreased in liver but increased in skeletal muscle of 12 week old diabetic ZDF rats.These results suggest that impairment of hepatic lipogenesis accompanied with the reduced lipogenesis of adipose tissue may contribute to development of diabetes in ZDF rats by increasing lipogenesis in skeletal muscle. Moreover, expression of antioxidant defense genes was decreased in the liver of 12-week old diabetic ZDF rats as well as in the adipose tissue of ZDF rats both at 6 and 12 weeks of age. Cytochrome P450 (CYP) genes were also significantly reduced in 12 week old diabetic liver of ZDF rats. Genes involved in glucose utilization were downregulated in skeletal muscle of diabetic ZDF rats, and the hepatic gluconeogenic gene was upregulated in diabetic ZDF rats. Genes commonly expressed in all three tissue types were also observed. These profilings might provide better fundamental understanding of insulin resistance and development of type 2 diabetes.

Genetic associations of fatty acid composition with exonic single nucleotide polymorphisms (SNPs) in the gene encoding fatty acid synthase (FASN) were examined using 513 Korean cattle. All five individual SNPs of g.12870 T>C, g.13126 T>C, g.15532 C>A, g.16907 T>C and g.17924 G>A were associated with a variety of fatty acid compositions and further with marbling score (P < 0.05). Their genotypes of CC, TT, AA, TT, and GG were associated with increased monounsaturated fatty acids and with decreased saturated fatty acids (P < 0.05). The genotypes at all the SNPs also increased marbling score (P < 0.05). Further genetic associations with fatty acid composition suggested that homozygous genotype with the haplotype of ATG at g.15532, g.16907, and g.17924 in a linkage disequilibrium block increased monounsaturated fatty acids and marbling score (P < 0.05). We concluded that the five exonic SNPs of g.12870, g.13126, g.15532, g.16907, and g.17924 in the FASN gene could change fatty acid contents. Their genotypes of CC, TT, AA, TT, and GG and haplotype of ATG at g.15532, g.16907, and g.17924 were recommended for genetic improvement of beef quality.

We examined the genetic associations of previously identified sequence variants with type 2 diabetes mellitus (T2DM) and its potentially genetic heterogeneity by gender in a large-scale cohort. A total of 613 T2DM patients and 8221 control subjects from the Korea Association REsource (KARE) cohort were included in the analysis of genetic association of T2DM with 33 nucleotide polymorphic markers identified by previous studies. The association analysis was further conducted with data partitioned by gender. The association analysis resulted in five nucleotide sequence variants associated with the susceptibility of T2DM after Bonferonni correction (Po0.0015). One was located near the gene of hematopoietically expressed homeobox (HHEX), and the others were all in the gene of cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1). Further analysis revealed that the sequence variant (rs5015480) near HHEX and two SNPs (rs7756992 and rs9465871) in CDKAL1 were associated with the susceptibility of T2DM in females (Po0.005), but not in males (P40.005). We suggested heterogeneous genetic associations of the T2DM susceptibility with the CDKAL1 and HHEX genes by gender.

The FAM134B and TNFRSF19 showed a dramatically strong synergistic epistasis in explaining the genetic dissection of the susceptibility to complex VD.

Associations of carcass phenotypes with genes regulating fat and energy metabolism involved in adaptive thermogenesis were examined in beef cattle. Carcass weight (CW) was found to be associated with MAP2K6 and UCP2 genes; back fat thickness (BFT) was found to be associated with PPARGC1A, MAP2K6, and UCP2 genes; marbling score (MS) was found to be associated with PPARGC1A and MAP2K6 genes; and eye-muscle area (EMA) was found to be associated only with UCP2 gene (P < 0.05). Further analyses found significant associations of interactions between PPARGC1A and MAP2K6 genes with CW and MS. Especially, interactive genetic associations were identified between c.424 and 222 G>A in PPARGC1A and c.17-10118 T>G in MAP2K6 and between c.228+28619 A>G in PPARGC1A and c.17-10118 T>G in MAP2K6, and they were both detected for CW and MS at a significant level (P < 0.05). The current study suggested that the individual and interactive associations of PPARGC1A, MAP2K6, and UCP2 genes with carcass phenotypes might be resulted from the pathway with fat and energy metabolism through the adaptive thermogenesis.

We suggested a novel association of the VaD susceptibility with an intronic variant of rs290227 in the SYK gene. Its Gallele could render mature transcripts inappropriately by intron retention and thus lead to a genetic risk for VaD.

We examined genetic associations of previously identified sequence variants with bone mineral density and their heterogeneity by gender. Large-scale cohort data were used including a total of 8,419 subjects (4,034 males and 4,385 females) from the Korean Association REsource (KARE) cohort. Bone speed of sound (SOS) values were measured at distal radius or mid-shaft tibia by quantitative ultrasound. Genotypic associations of SOS were tested with each of nucleotide sequence variants identified by previous studies. The genetic association analysis revealed that 2 out of 11 nucleotide sequence variants were associated with SOS (rs1721400, rs7776725, P < 7.58 × 10(-4)). Further analysis with partitioning data by gender showed that the mid-shaft tibia phenotypes were associated with the rs1721400 and rs7776725 in females (P < 3.79 × 10(-4)), but not in males (P > 3.79 × 10(-4)). The current study suggested female-specific associations of rs1721400 and rs7776725 with bone mineral density and heterogeneity of genetic association by skeletal site measured for bone mineral density.

A simulation study was conducted to provide a practical guideline for experimental designs with the Bayesian approach using Gibbs sampling (BAGS), a recently developed method for estimating interaction among multiple loci. Various data sets were simulated from combinations of number of loci, within-genotype variance, sample size, and balance of design. Mean square prediction error (MSPE) and empirical statistical power were obtained from estimating and testing the posterior mean estimate of combination genotypic effect. Simultaneous use of both MSPE and power was suggested to find an optimal design because their correlation estimate (-0.8) would not be large enough to ignore either of them. The optimal sample sizes with MSPE >2.0 and power >0.8 with the within-genotype variance of 30 were 135, 675, and >8100 for 2-, 3-, and 4-locus unbalanced data. The BAGS was suggested for interaction effects among limited number (4 or less) of loci in practice. A practical guideline for determining an optimal sample size with a given power or vise versa is provided for BAGS.