Identification of Candidate Causal Polymorphisms in GGT1 and SLC5A1 Associated with Fat Area Ratio on BTA17 in Japanese Black Cattle

日本黑牛BTA17脂肪面积比相关的GGT1和SLC5A1基因候选致病多态性的鉴定

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Abstract

Background/Objectives: Intramuscular fat deposition is a key determinant of beef quality in Japanese Black cattle, and the fat area ratio of the rib eye (FAR) is highly correlated with Beef Marbling Standard scores. Methods: To identify genetic variants underlying variation in the FAR, we conducted a genome-wide association study (GWAS) followed by whole-genome sequence–based fine mapping in a Hyogo Japanese Black population (n = 432). Animals were genotyped using the Illumina BovineSNP50v3 BeadChip, and association analysis was performed using residuals derived from a linear mixed model accounting for fixed and random effects. Results: A significant association signal was detected on BTA17 (λ = 1.09), with the top single nucleotide polymorphism (SNP) located at 17:72,329,662 (p = 3.60 × 10(−6)). To refine the candidate region, we analyzed whole-genome resequencing data from 42 Hyogo Japanese Black cattle and identified a distinct linkage disequilibrium (LD) block spanning 71–74 Mbp on BTA17. Among 4292 variants within genes showing LD (r(2) ≥ 0.1) with the top SNP, 96 variants with strong LD and predicted functional effects were selected for validation. Genotyping in the Hyogo population revealed that a missense variant in gamma-glutamyltransferase 1 (GGT1) (c.589G>A, p.Asp197Asn) showed the strongest association with FAR (p = 3.89 × 10(−6)). A 5′UTR variant in GGT1 (c. −256G>T) and a missense variant in solute carrier family 5 member 1 (SLC5A1) (c.32C>T, p.Thr11Met) also exhibited significant associations and strong LD with the top SNP (r(2) > 0.7). GGT1 is involved in glutathione metabolism, whereas SLC5A1 encodes a sodium–glucose cotransporter implicated in nutrient sensing and metabolic regulation. Conclusions: Although functional validation is required, these variants represent strong positional and biological candidates underlying the BTA17 quantitative trait loci (QTL). The identified polymorphisms may provide useful molecular markers for optimizing genetic improvement of marbling-related traits within the Hyogo Japanese Black population.

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