联合全基因组关联和转录组分析为绵羊生长速度提供分子见解

doi:10.1016/j.jia.2024.08.011

摘要/Abstract

摘要：

利用综合多组学分析方法研究与绵羊生长速度相关的关键基因和遗传标记可以为养羊业提供有价值的见解。在本研究中，基于平均日增重（ADG），我们选择快生长型（N_case=70）和慢生长型（N_control=70）湖羊用于全基因组关联分析（GWAS）；并选择10只湖羊（快生长型，n = 5；慢生长型，n = 5）和10只杜泊羊（快生长型，n = 5；慢生长型，n = 5）用于比较转录组分析（RNA-Seq）。分别利用加权基因共表达网络分析（WGCNA）和来自10种组织的转录组测序数据鉴定了核心基因（Hub genes）和组织特异性基因（TSGs）。研究结果表明，GWAS分析共鉴定到10个与绵羊生长速度显著关联的基因（LOC106990525, BRINP3, DSCAML1, CEP164, TOX, BMP1, PHYHIP, SFTPC, LGI3, REEP4）；基于比较转录组分析，在HF vs. HS 与DF vs. DS比较对中分别鉴定出501和441个差异表达基因（DEGs）。功能富集分析显示，一些重要的信号通路与脂肪代谢和能量代谢相关，如“脂肪细胞中脂肪分解的调节（regulation of lipolysis in adipocytes）”、“氧化磷酸化（Oxidative phosphorylation）”、“产热（Thermogenesis）”；一些与脂肪沉积（如ADRB3, PDE3B, FABP4, SERPINE1, PLIN1, FOXO6）和肌肉发育（如MYL3）相关的DEGs也被鉴定到。使用WGCNA分析鉴定到了15个被认为是与绵羊平均日增重（ADG）相关的核心基因（INPP5K, ZNF692, MAN2C1, PPP1R12C, SLC27A5, LRP3, PPP6R1, BRF1, EN1, AMBRA1, LITAF, PARVA, TGFBR3, YWHAQ, DCN）。联合GWAS和RNA-Seq数据表明，BRINP3和PENK基因可能通过调节绵羊的摄食行为而进一步影响其生长速度。进一步在1071只湖羊群体中进行关联分析，结果显示，BRINP3 g.16903465 T>C与PENK g.39289926 T>C突变位点均与湖羊生长性状显著相关（P < 0.05）。因此，BRINP3和PENK基因可能是与绵羊生长速度相关的潜在关键候选基因，我们的研究为理解绵羊生长性状相关的分子机制提供了新的见解。

Abstract:

Investigating genetic markers and key genes associated with sheep growth rate using integrated multi-omics approaches could provide valuable insights for the sheep industry. Based on the average daily gain (ADG), fast-growing (N_case=70) and slow-growing (N_control=70) Hu sheep were selected for a genome-wide association study (GWAS). Ten Hu sheep (fast-growing, n=5; slow-growing, n=5) and ten Dorper sheep (fast-growing, n=5; slow-growing, n=5) were selected for comparative transcriptome analysis. We identified hub genes and tissue-specific genes (TSGs) using weighted gene co-expression network analysis (WGCNA) and RNA sequencing (RNA-Seq) data from ten tissues, respectively. Ten genes were found within 50 kb distances of the significant single nucleotide polymorphisms (SNPs). Based on a comparative transcriptomic analysis, a total of 501 and 441 differentially expressed genes (DEGs) were identified in the HF vs. HS and DF vs. DS comparisons, respectively. We found some important signaling pathways closely associated with fat metabolism and energy metabolism, such as “regulation of lipolysis in adipocytes”, “Oxidative phosphorylation”, and “Thermogenesis”. Several DEGs play a crucial role in fat deposition (such as ADRB3, PDE3B, FABP4, SERPINE1, PLIN1, and FOXO6) and muscle development (MYL3). Using the WGCNA analysis, 15 genes were considered as hub genes associated with ADG. Integration of GWAS and RNA-Seq data indicates that BRINP3 and PENK may further influence the growth rate by regulating feeding behavior in sheep. Association analysis of 1,071 Hu sheep populations revealed that mutations in the BRINP3 (BRINP3 g.16903465 T>C) and PENK (PENK g.39289926 T>C) genes were significantly related to the growth traits (P<0.05). Our research provides novel insights into understanding the molecular mechanisms underlying growth traits in sheep. BRINP3 and PENK genes may be potential key candidate genes related to sheep growth rate.

Key words: Sheep growth rate , GWAS , Transcriptomic , BRINP3 , PENK

. 联合全基因组关联和转录组分析为绵羊生长速度提供分子见解[J]. Journal of Integrative Agriculture, DOI: 10.1016/j.jia.2024.08.011.

Liming Zhao, Fadi Li, Xiaoxue Zhang, Lvfeng Yuan, Huibin Tian, Dan Xu, Deyin Zhang, Yukun Zhang, Yuan Zhao, Kai Huang, Xiaolong Li, Jiangbo Cheng, Zongwu Ma, Quanzhong Xu, Xiaobin Yang, Kunchao Han, Xiuxiu Weng, Weimin Wang. Integrating genome-wide association and transcriptome analysis to provide molecular insights into growth rates in sheep[J]. Journal of Integrative Agriculture, DOI: 10.1016/j.jia.2024.08.011.

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