X-linked spinal and bulbar muscular atrophy (SBMA), a motor neuron disease associated with androgen insensitivity, is caused by androgen receptor gene mutations with an increased number of tandem CAG repeats in exon 1. We investigated the increased number of CAG repeats in androgen receptor genes of 19 SBMA patients and found that this correlated strongly with the age at onset of muscle weakness. Thus, SBMA is the first genetic disease in which a strong correlation between the degree of genetic abnormality (number of CAG tandem repeats) and clinical phenotypic expression is demonstrable. The results further indicate that androgen gene mutation is directly involved in the degeneration of motor neurons.

The importance of genotype x environment (region or management system) interactions for carcass traits in Japanese Black cattle was investigated using both univariate and multivariate animal models. The univariate approach was used mainly to test the significance of interaction effects. The multivariate approach was used to estimate genetic correlations, which indicated the magnitude of genotype x environment (GE) interactions. The more a genetic correlation deviates from 1, the larger the interaction. From the univariate approach, the addition of genotype x environment (region or management system) interaction (co)variance components resulted in an improved fit of the model for all traits in both cases (P < 0.001). However, estimates of genetic correlation between regions obtained from the multivariate approach for hot carcass weight, LM area, rib thickness, s.c. fat thickness, and marbling score were 0.97, 0.95, 0.93, 0.97, and 0.93, respectively. The corresponding estimates between management systems were 0.84, 0.92, 0.84, 0.90, and 0.97, respectively. These results indicate that GE interaction effects on carcass traits of Japanese Black cattle may be biologically unimportant. Therefore, breeding values obtained using the multivariate method would rank sires similarly in all environments. Consequently, carcass traits measured in these two different regions or management systems can be treated as the same traits.

BackgroundCalving efficiency can be described as the measure of a cow’s ability to produce viable offspring within a specific period of time. This trait is crucial in beef cattle because calves are necessary both for the production of beef and for heifer replacements. Recently, the number of calves produced at 4 years of age (NCP4) has been used to evaluate the calving efficiency of Japanese Black cattle. To identify variants associated with calving efficiency in Japanese Black cattle, we conducted a genome-wide association study (GWAS) using 688 animals with extreme NCP4 values selected from 15,225 animals.ResultsWe identified genetic variants on bovine chromosome 12 (BTA12) that were associated with NCP4. The General Transcription Factor IIF, polypeptide 2 (GTF2F2), located in the 132 kbp-associated region, proved to be in strong linkage disequilibrium. We found 15 associated variants in the promoter and the 3' UTR regions. Consistent with this finding, transcripts of GTF2F2 derived from the haplotype (Q) with the increased number of calves were 1.33-fold more abundant than q-derived transcripts. Furthermore, luciferase assays revealed that the activity of the 3' UTR, a region that includes nine SNPs, was higher in constructs with the Q haplotype than in those with the q haplotype by approximately 1.35-fold. In contrast, the activity of the promoter region did not differ between haplotypes. The association was replicated in an independent sample of 827 animals that were randomly selected from the remainder of the cohort from the same farms used in the GWAS. In the replicated population, the frequency of the Q haplotype is 0.313, and this haplotype accounts for 2.69% of the total phenotypic variance. The effect of the Q to q haplotype substitution on NCP4 was 0.054 calves. These findings suggest that variants in the 3' UTR of GTF2F2 affect the level of GTF2F2 mRNA, which is associated with calving efficiency.ConclusionsThis GWAS has identified variants in the 3’ UTR of GTF2F2 that were associated with the NCP4 of Japanese Black cattle, and this association was validated in an independent sample. The Q haplotype will be immediately useful in improving the calving efficiency of Japanese Black cattle.

Abstract. Klotho is known as an anti-aging gene. We previously reported that the expression of Klotho is a postoperative prognostic factor for patients with lung large cell neuroendocrine carcinoma and lung small cell carcinoma. Recently, Klotho was shown to suppress the epithelial-mesenchymal transition (EMT). In the present study, we examined the association between the expression of Klotho and the regulation of EMT in lung squamous cell carcinoma. We immunohistochemically examined the expression of Klotho in patients with lung squamous cell carcinoma who had undergone surgical resection or photodynamic therapy. The immunohistochemical analysis showed that Klotho expression was observed not only in normal bronchial epithelial cells, but also in centrally located early lung cancers, which were all carcinomas in situ and were treated using PDT. However, in lung cancer patients with invasive and or advanced squamous cell carcinoma who had undergone a complete surgical resection, Klotho expression was observed in only 4 patients (13%). To elucidate the associations between the expression of Klotho and the expressions of EMT-related proteins, such as E-cadherin, N-cadherin, vimentin, and Snail, we transiently transfected GFP-Klotho plasmid DNA into the human squamous lung cancer cell line SQ5 and examined the expressions of these proteins of GFP-positive cells after sorting using flow cytometry. In SQ5 cells overexpressing GFP-Klotho, the expression of N-cadherin, which is a mesenchymal marker, was completely inhibited, compared with that in SQ5 cells transfected with the GFP vector. The overexpression of Klotho did not affect the regulation of either other mesenchymal markers (such as vimentin and Snail) or the regulation of an epithelial marker (E-cadherin). We concluded that the expression of Klotho was related to the degree of cancer invasiveness and that Klotho inhibits the expression of N-cadherin and regulates the EMT in lung cancer.

The objectives of this study were to estimate genetic parameters for gestation length (GL), including estimation of maternal effects, and to investigate the genetic relationships of GL with birth weight and carcass traits in a Japanese Black cattle population. The original data comprised 34 775 records of animals born from October 1999 to August 2003. Two different models were used to analyze the data for GL. The first model (M1) included direct genetic effect of the calf and maternal genetic effect as random effects. The second model (M2) treated GL as a trait of the dam and included direct genetic effects only. M1 was used in bi‐variate analysis. The direct and maternal heritabilities for GL estimated from M1 were 0.53 and 0.14, respectively. This result shows that GL is moderately inherited and can be controlled genetically. The direct × maternal genetic correlation for GL was −0.73. Direct genetic correlations of GL with carcass traits were close to zero. However, genetic correlation of maternal GL with carcass weight was moderate (0.25).