背景:调节变体的表征(例如,基因表达数量性状基因座,eQTL;基因剪接QTL,sQTL)对于生物学解释与复杂性状相关的基因座的分子机制至关重要。然而,奶牛的监管变体,特别是在特定的生物学环境中(例如,不同的泌乳阶段),基本上是未知的。在这项研究中,我们研究了101头荷斯坦奶牛在泌乳早期至中期(产牛后22-150天)收集的全血样本中的调控变异,并对其进行了分析,以破译奶牛复杂性状的调控机制.
结果:我们鉴定了在101头牛的白细胞中表达的14,303个基因和227,705个内含子簇。顺式SNP解释的基因表达和内含子切除率的平均遗传力分别为0.28±0.13和0.25±0.13。我们在泌乳早期至中期的奶牛中鉴定了23,485个SNP基因表达对和18,166个SNP内含子簇对。与牛基因型组织表达图集(CattleGTEx)中报道的血液中存在的2,380,457个顺式eQTL相比,本研究仅检测到6,114个顺式eQTLs(P<0.05)。通过对cis-e/sQTL和4个性状的全基因组关联研究(GWAS)结果进行共定位分析,我们确定了DGAT1基因的cis-e/sQTL(rs109421300),它可能是泌乳早期到中期的关键标记,脂肪产量,蛋白质产量,和体细胞评分(PP4>0.6)。最后,全转录组关联研究(TWAS)揭示了某些基因(例如,FAM83H和TBC1D17)在白细胞中的表达与复杂性状显着相关(P<0.05)。
结论:这项研究调查了泌乳早期到中期奶牛基因表达和可变剪接的遗传调控,并为具有经济重要性的复杂性状的调控机制提供了新的见解。
BACKGROUND: Characterization of regulatory variants (e.g., gene expression quantitative trait loci, eQTL; gene splicing QTL, sQTL) is crucial for biologically interpreting molecular mechanisms underlying loci associated with complex traits. However, regulatory variants in dairy cattle, particularly in specific biological contexts (e.g., distinct lactation stages), remain largely unknown. In this study, we explored regulatory variants in whole blood samples collected during early to mid-lactation (22-150 days after calving) of 101 Holstein cows and analyzed them to decipher the regulatory mechanisms underlying complex traits in dairy cattle.
RESULTS: We identified 14,303 genes and 227,705 intron clusters expressed in the white blood cells of 101 cattle. The average heritability of gene expression and intron excision ratio explained by cis-SNPs is 0.28 ± 0.13 and 0.25 ± 0.13, respectively. We identified 23,485 SNP-gene expression pairs and 18,166 SNP-intron cluster pairs in dairy cattle during early to mid-lactation. Compared with the 2,380,457 cis-eQTLs reported to be present in blood in the Cattle Genotype-Tissue Expression atlas (CattleGTEx), only 6,114 cis-eQTLs (P < 0.05) were detected in the present study. By conducting colocalization analysis between cis-e/sQTL and the results of genome-wide association studies (GWAS) from four traits, we identified a cis-e/sQTL (rs109421300) of the DGAT1 gene that might be a key marker in early to mid-lactation for milk yield, fat yield, protein yield, and somatic cell score (PP4 > 0.6). Finally, transcriptome-wide association studies (
TWAS) revealed certain genes (e.g., FAM83H and TBC1D17) whose expression in white blood cells was significantly (P < 0.05) associated with complex traits.
CONCLUSIONS: This study investigated the genetic regulation of gene expression and alternative splicing in dairy cows during early to mid-lactation and provided new insights into the regulatory mechanisms underlying complex traits of economic importance.