奶牛泌乳早期至中期全血基因表达和剪接数量性状位点的鉴定和特征分析。

Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle.

机构信息

Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture & National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.

State Key Laboratory of Swine and Poultry Breeding Industry, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.

出版信息

BMC Genomics. 2024 May 6;25(1):445. doi: 10.1186/s12864-024-10346-7.

DOI:10.1186/s12864-024-10346-7

PMID:38711039

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11075310/

Abstract

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.

摘要

背景

调控变体（如基因表达数量性状位点（eQTL）、基因剪接 QTL（sQTL））的特征对于从与复杂性状相关的基因座的生物学角度解释分子机制至关重要。然而，奶牛中的调控变体，特别是在特定的生物背景下（例如，不同的泌乳阶段），仍然知之甚少。在这项研究中，我们探索了 101 头荷斯坦奶牛泌乳中期（产后 22-150 天）采集的全血样本中的调控变体，并对其进行分析，以揭示奶牛复杂性状的调控机制。

结果

我们鉴定了 101 头牛白细胞中表达的 14303 个基因和 227705 个内含子簇。顺式单核苷酸多态性（cis-SNPs）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。我们鉴定了泌乳中期奶牛中的 23485 个 SNP-基因表达对和 18166 个 SNP-内含子簇对。与牛基因型组织表达图谱（CattleGTEx）中报道的存在于血液中的 2380457 个顺式 eQTL 相比，本研究仅检测到 6114 个顺式 eQTL（P<0.05）。通过对四个性状的顺式 e/sQTL 与全基因组关联研究（GWAS）结果之间的共定位分析，我们鉴定了 DGAT1 基因的 cis-e/sQTL（rs109421300），可能是泌乳中期产奶量、脂肪产量、蛋白质产量和体细胞评分（PP4>0.6）的关键标记。最后，全转录组关联研究（TWAS）揭示了某些基因（如 FAM83H 和 TBC1D17），其在白细胞中的表达与复杂性状显著相关（P<0.05）。