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全基因组关联研究及后续功能分析揭示了仔猪腹泻的潜在调控机制。

Genome-wide association study and subsequent functional analysis reveal regulatory mechanism underlying piglet diarrhea.

作者信息

Chen Dong, Shen Qi, Huang Rui, Zhao Zhenjian, Yu Yang, Cui Shengdi, Wang Junge, Chen Ziyang, Wu Pingxian, Tang Guoqing

机构信息

State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 625014, China.

Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 625014, China.

出版信息

Anim Biosci. 2025 Apr;38(4):612-628. doi: 10.5713/ab.24.0547. Epub 2024 Oct 28.

Abstract

OBJECTIVE

Piglet diarrhea poses a serious threat to piglet health and the livestock economy, and is one of the most pressing problems in animal husbandry. This study aims to investigate the genetic factors involved in piglet diarrhea and to identify key genes that regulate this condition.

METHODS

We screened 600 diarrheal piglets based on unique diarrhea scores for resequencing and conducted a genome-wide association study (GWAS). Through this process, we identified 308 single nucleotide polymorphisms (SNPs) and annotated 151 candidate genes. Extensive functional validation and systematic analysis were performed on key candidate genes KSR1, SKAP1, SLC35F6, and OR12.

RESULTS

The study found that the four key genes were involved in the regulation of piglet diarrhea through various mechanisms. OR12 affects the levels of ZO-1 and claudin-1. Changes in the expression levels of KSR1 could alter the expression of IL1-β, IL6, and TNF-α, as well as cell migration and proliferation. SKAP1 could affect the expression of CD3 and CD4, and influence the migration and proliferation ability of cells. SLC35F6 is involved in cell apoptosis through the Bcl2/BAX/caspase3 pathway and can also affect mitochondrial membrane potential.

CONCLUSION

The results of this study provide strong support for breeding programs aimed at disease resistance and offer potential solutions to the problem of piglet diarrhea.

摘要

目的

仔猪腹泻对仔猪健康和畜牧业经济构成严重威胁,是畜牧业中最紧迫的问题之一。本研究旨在调查仔猪腹泻涉及的遗传因素,并确定调节这种状况的关键基因。

方法

我们根据独特的腹泻评分筛选了600头腹泻仔猪进行重测序,并进行了全基因组关联研究(GWAS)。通过这个过程,我们鉴定了308个单核苷酸多态性(SNP),并注释了151个候选基因。对关键候选基因KSR1、SKAP1、SLC35F6和OR12进行了广泛的功能验证和系统分析。

结果

研究发现这四个关键基因通过多种机制参与仔猪腹泻的调节。OR12影响紧密连接蛋白1(ZO-1)和闭合蛋白1(claudin-1)的水平。KSR1表达水平的变化可改变白细胞介素1-β(IL1-β)、白细胞介素6(IL6)和肿瘤坏死因子-α(TNF-α)的表达,以及细胞迁移和增殖。SKAP1可影响CD3和CD4的表达,并影响细胞的迁移和增殖能力。SLC35F6通过Bcl2/BAX/半胱天冬酶3途径参与细胞凋亡,还可影响线粒体膜电位。

结论

本研究结果为抗病育种计划提供了有力支持,并为仔猪腹泻问题提供了潜在的解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f479/11917426/c3c6d4015f91/ab-24-0547f1.jpg

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