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Sugimoto M.,National Livestock Breeding Center | Gotoh Y.,Holstein Cattle Association of Japan | Kawahara T.,Holstein Cattle Association of Japan | Sugimoto Y.,Shirakawa Institute of Animal Genetics
PLoS ONE | Year: 2015

Conception rates among dairy cows in Japan have declined in recent decades. To enhance our understanding of the genes involved in conception rates, we conducted a genome-wide association study (GWAS) using 822 Holsteins and identified a single-nucleotide polymorphism (SNP) associated with conception rate: A+169G in the 3' untranslated region (UTR) of unc-5 homolog C (UNC5C). Cows with higher conception rates carried the A polymorphism in the UNC5C 3'UTR. Luciferase assays and quantitative analysis of allele ratios revealed that UNC5C transcripts with the A polymorphism were expressed at higher levels than those carrying the G polymorphism. UNC5C transmits either pro- or anti-apoptotic signals depending on the availability of its ligand, Netrin-1. UNC5C expression is negatively regulated by reproductive homeobox X-linked 5 (Rhox5), and the Rhox5 locus is methylated by G9a methyltransferase. G9a-knockout mice have previously been demonstrated to be subfertile, and we found that UNC5C, G9a, and Netrin-1 expression levels increased from the 4-cell stage to the blastocyst stage in fertilized murine embryos, whereas Rhox5 expression decreased. Repression of UNC5C, G9a, or Netrin-1 or forced expression of Rhox5 in the anterior nucleus stage inhibited development to the blastocyst stage, suggesting that cows carrying the G polymorphism in UNC5C might have lower conception rates because of the poor development of preimplantation embryos. This study provides novel insights into the role of UNC5C during embryonic development. Copyright: © 2015 Sugimoto et al. Source

Sugimoto M.,National Livestock Breeding Center | Sugimoto Y.,Shirakawa Institute of Animal Genetics
G3: Genes, Genomes, Genetics | Year: 2012

Mastitis is a common infectious disease of the mammary gland and generates large losses in the dairy industry. By means of positional cloning and functional analysis techniques, we here show that insulin-like growth factor 1 receptor (IGF1R) can possibly mediate susceptibility to mastitis through autophagy. Scanning the whole genome of cows (Bos taurus) that were susceptible or resistant to mastitis in the half-sib families revealed that susceptible cows had a relatively long stretch of cytosine residues (C stretch) in the 59 untranslated region of IGF1R. The forebrain embryonic zinc finger-like (FEZL) transcription factor, which was previously identified as a factor controlling mastitis resistance in the same half-sib families, bound the C stretch of IGF1R. The susceptible type of FEZL with a glycine stretch containing 13 glycines (13G) and the longer C stretch of IGF1R together enhanced expression of IGF1R. Enhancing IGF1R inhibited autophagy in response to Streptococcus agalactiae invasion of mammary epithelial cells, whereas treatment with rapamycin, a known inducer of autophagy, rescued it. Cows carrying the variant combination of 13GFEZL might be more susceptible to mastitis as the result of impaired autophagy. Our results suggest that IGF1R could control innate immunity in mammals and serve as a potential tool for preventing mastitis. © 2012 Sugimoto, Sugimoto. Source

Sasaki S.,Shirakawa Institute of Animal Genetics | Sasaki S.,National Livestock Breeding Center | Ibi T.,Okayama University | Ikeda S.,Cattle Breeding Development Institute of Kagoshima Prefecture | Sugimoto Y.,Shirakawa Institute of Animal Genetics
Animal Genetics | Year: 2014

Age at first calving (AFC) is an important trait for achieving earlier reproductive performance in cattle. To identify quantitative trait loci for AFC in Japanese Black cattle, we conducted a genome-wide association study using 866 animals with extreme AFC values selected from a larger group of 52 009 animals. We identified single nucleotide polymorphisms (SNPs) on bovine chromosome 2 that were associated with AFC. These SNPs were located within 112.8-kbp intronic region of delta/notch-like EGF repeat containing (DNER) and proved to be in a state of high linkage disequilibrium. The association was replicated in an independent sample of 2963 animals. In the replicated population, the frequency of the reduced AFC allele (Q) was 0.463, and the allele accounts for 8% of the total genetic variance. The effect of allele substitution on AFC was a decrease of 11.54 days. The results suggest that the Q allele could serve as a useful marker in Japanese Black cattle to select animals with superior AFC performance. © 2013 Stichting International Foundation for Animal Genetics. Source

Sugimoto M.,National Livestock Breeding Center | Watanabe T.,Shirakawa Institute of Animal Genetics | Sugimoto Y.,Shirakawa Institute of Animal Genetics
PLoS ONE | Year: 2012

Dystocia is a major problem for the dairy cattle industry, and the observed high rates of this condition stem from genetic selection to increase subsequent milk production of the calving female. Because smaller birth size does not adversely affect subsequent milk production, selecting for cows with a smaller birth size would reduce dystocia rates and be beneficial for both the cattle and the farmers. To identify genes that regulate birth weight, we conducted a genome-wide association study using 1151 microsatellite markers and identified a single nucleotide polymorphism (SNP) associated with birth weight: A-326G in the 5′ untranslated region (UTR) of solute carrier family 44, member 5 (SLC44A5). Cows with higher birth weights carried the A polymorphism in the SLC44A5 5′ UTR, and the presence of the A polymorphism correlated with a high rate of dystocia. Luciferase assays and quantitative polymerase chain reaction (QPCR) assays revealed that SLC44A5 transcripts with the A polymorphism are expressed at lower levels than those carrying the G polymorphism. SLC44A5 encodes a choline transporter-like protein, and choline is a component of the major phospholipids of cell membranes. Uptake studies in HeLa cells demonstrated that SLC44A5 knockdown reduces choline efflux, whereas SLC44A5 overexpression resulted in the opposite effect. Furthermore, cell viability assays indicated that SLC44A5 knockdown increased cell proliferation, whereas SLC44A5 overexpression repressed proliferation. Taken together, our results suggest that calves with reduced SLC44A5 expression are larger due to enhanced cell proliferation. This study provides novel insights into the molecular mechanisms that control birth weight in Holsteins and suggests that SLC44A5 may serve as a potential target for preventing dystocia. © 2012 Sugimoto et al. Source

Ogawa S.,Kyoto University | Matsuda H.,Kyoto University | Taniguchi Y.,Kyoto University | Watanabe T.,National Livestock Breeding Center | And 3 more authors.
BMC Genetics | Year: 2014

Background: Japanese Black cattle are a beef breed whose meat is well known to excel in meat quality, especially in marbling, and whose effective population size is relatively low in Japan. Unlike dairy cattle, the accuracy of genomic evaluation (GE) for carcass traits in beef cattle, including this breed, has been poorly studied. For carcass weight and marbling score in the breed, as well as the extent of whole genome linkage disequilibrium (LD), the effects of equally-spaced single nucleotide polymorphisms (SNPs) density on genomic relationship matrix (G matrix), genetic variance explained and GE were investigated using the genotype data of about 40,000 SNPs and two statistical models.Results: Using all pairs of two adjacent SNPs in the whole SNP set, the means of LD (r2) at ranges 0-0.1, 0.1-0.2, 0.2-0.5 and 0.5-1 Mb were 0.22, 0.13, 0.10 and 0.08, respectively, and 25.7, 13.9, 10.4 and 6.4% of the r2 values exceeded 0.3, respectively. While about 90% of the genetic variance for carcass weight estimated using all available SNPs was explained using 4,000-6,000 SNPs, the corresponding percentage for marbling score was consistently lower. With the conventional linear model incorporating the G matrix, correlation between the genomic estimated breeding values (GEBVs) obtained using 4,000 SNPs and all available SNPs was 0.99 for carcass weight and 0.98 for marbling score, with an underestimation of the former GEBVs, especially for marbling score.Conclusions: The Japanese Black is likely to be in a breed group with a relatively high extent of whole genome LD. The results indicated that the degree of marbling is controlled by only QTLs with relatively small effects, compared with carcass weight, and that using at least 4,000 equally-spaced SNPs, there is a possibility of ranking animals genetically for these carcass traits in this breed. © 2014 Ogawa et al.; licensee BioMed Central Ltd. Source

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