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Simple Summary: The embryos from Japanese Black cows are used for embryo transfer in Japan, which could contribute to obtaining a greater number of fattened progenies from dams with superior genetic abilities for the sustainable supply of high-quality Wagyu beef. We previously reported the possibility of genetically improving the in vivo embryo production performance of Japanese Black donor cows. We performed single-step genomic prediction of breeding values for superovulatory response traits in Japanese Black donor cows using genome-wide single-nucleotide polymorphism markers. The results indicate that introducing the single-step genomic prediction scheme could allow more effective selection for superovulatory response traits at a younger age of donor cows, and it might achieve more efficient genetic improvements than breeding value prediction based on only pedigree information. To the best of our knowledge, this is the first study performing single-step genomic prediction of female reproductive traits in Japanese Black cattle. In future work, an approach suitable for managing genetic diversity while continuing sound selection should be developed. We assessed the performance of single-step genomic prediction of breeding values for superovulatory response traits in Japanese Black donor cows. A total of 25,332 records of the total number of embryos and oocytes (TNE) and the number of good embryos (NGE) per flush for 1874 Japanese Black donor cows were collected during 2008 and 2022. Genotype information on 36,426 autosomal single-nucleotide polymorphisms (SNPs) for 575 out of the 1,874 cows was used. Breeding values were predicted exploiting a two-trait repeatability animal model. Two genetic relationship matrices were used, one based on pedigree information (A matrix) and the other considering both pedigree and SNP marker genotype information (H matrix). Estimated heritabilities of TNE and NGE were 0.18 and 0.11, respectively, when using the H matrix, which were both slightly lower than when using the A matrix (0.26 for TNE and 0.16 for NGE). Estimated genetic correlations between the traits were 0.61 and 0.66 when using H and A matrices, respectively. When the variance components were the same in breeding value prediction, the mean reliability was greater when using the H matrix than when using the A matrix. This advantage seems more prominent for cows with low reliability when using the A matrix. The results imply that introducing single-step genomic prediction could boost the rate of genetic improvement of superovulatory response traits, but efforts should be made to maintain genetic diversity when performing selection. [ABSTRACT FROM AUTHOR]

Summary: Inherited genetic variation is associated with 6‐mercaptopurine (6‐MP) dose reduction and frequent toxicities induced by 6‐MP. However, the tolerable dose for 6‐MP is not fully predicted by the known variation in NUDT15 and TPMT among Asian children with acute lymphoblastic leukaemia (ALL). We performed a genome‐wide association study (GWAS) related to 6‐MP dose among Japanese children with ALL. This GWAS comprised 224 patients previously enrolled in Tokyo Children's Cancer Study Group clinical studies with replication attempted in 55 patients. Genome‐wide single nucleotide polymorphism (SNP) genotypes were evaluated for association with average 6‐MP dose during the initial 168 days of maintenance therapy. Possible associations were observed across five gene‐coding regions, among which only variants at 13q14.2 were significant and replicated genome‐wide (rs116855232, NUDT15, β = −10.99, p = 3.7 × 10−13). Notable findings were observed for variants in AFF3 (rs75364948, p = 2.05 × 10−6) and CHST11 (rs1148407, p = 2.09 × 10−6), but were not replicated possibly due to small numbers. A previously reported candidate SNP in MTHFR was associated with higher average 6‐MP dose (rs1801133, p = 0.045), and FOLH1 (rs12574928) was associated in an evaluation of candidate regions (padjust = 0.013). This study provides strong evidence that rs116855232 in NUDT15 is the genetic factor predominantly associated with 6‐MP tolerable dose in children in Japan. [ABSTRACT FROM AUTHOR]