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肉鸡对巨型艾美耳球虫反应的全基因组关联研究及生物通路分析

Genome-wide association study and biological pathway analysis of the Eimeria maxima response in broilers.

作者信息

Hamzić Edin, Buitenhuis Bart, Hérault Frédéric, Hawken Rachel, Abrahamsen Mitchel S, Servin Bertrand, Elsen Jean-Michel, Pinard-van der Laan Marie-Hélène, Bed'Hom Bertrand

机构信息

UMR1313 Animal Genetics and Integrative Biology Unit, AgroParisTech, 16 rue Claude Bernard, 75005, Paris, France.

UMR1313 Animal Genetics and Integrative Biology Unit, INRA, Domaine de Vilvert, 78350, Jouy-en-Josas, France.

出版信息

Genet Sel Evol. 2015 Nov 25;47:91. doi: 10.1186/s12711-015-0170-0.

Abstract

BACKGROUND

Coccidiosis is the most common and costly disease in the poultry industry and is caused by protozoans of the Eimeria genus. The current control of coccidiosis, based on the use of anticoccidial drugs and vaccination, faces serious obstacles such as drug resistance and the high costs for the development of efficient vaccines, respectively. Therefore, the current control programs must be expanded with complementary approaches such as the use of genetics to improve the host response to Eimeria infections. Recently, we have performed a large-scale challenge study on Cobb500 broilers using E. maxima for which we investigated variability among animals in response to the challenge. As a follow-up to this challenge study, we performed a genome-wide association study (GWAS) to identify genomic regions underlying variability of the measured traits in the response to Eimeria maxima in broilers. Furthermore, we conducted a post-GWAS functional analysis to increase our biological understanding of the underlying response to Eimeria maxima challenge.

RESULTS

In total, we identified 22 single nucleotide polymorphisms (SNPs) with q value <0.1 distributed across five chromosomes. The highly significant SNPs were associated with body weight gain (three SNPs on GGA5, one SNP on GGA1 and one SNP on GGA3), plasma coloration measured as optical density at wavelengths in the range 465-510 nm (10 SNPs and all on GGA10) and the percentage of β2-globulin in blood plasma (15 SNPs on GGA1 and one SNP on GGA2). Biological pathways related to metabolic processes, cell proliferation, and primary innate immune processes were among the most frequent significantly enriched biological pathways. Furthermore, the network-based analysis produced two networks of high confidence, with one centered on large tumor suppressor kinase 1 (LATS1) and 2 (LATS2) and the second involving the myosin heavy chain 6 (MYH6).

CONCLUSIONS

We identified several strong candidate genes and genomic regions associated with traits measured in response to Eimeria maxima in broilers. Furthermore, the post-GWAS functional analysis indicates that biological pathways and networks involved in tissue proliferation and repair along with the primary innate immune response may play the most important role during the early stage of Eimeria maxima infection in broilers.

摘要

背景

球虫病是家禽业中最常见且成本最高的疾病,由艾美耳属原生动物引起。目前基于使用抗球虫药物和疫苗来控制球虫病,分别面临诸如耐药性和高效疫苗开发成本高等严重障碍。因此,当前的控制方案必须通过诸如利用遗传学来改善宿主对艾美耳属感染的反应等补充方法加以扩展。最近,我们使用巨型艾美耳球虫对科宝500肉鸡进行了一项大规模攻毒研究,在此研究中我们调查了动物对攻毒反应的变异性。作为这项攻毒研究的后续,我们进行了全基因组关联研究(GWAS),以鉴定肉鸡对巨型艾美耳球虫反应中所测性状变异性的潜在基因组区域。此外,我们进行了GWAS后功能分析,以增强我们对巨型艾美耳球虫攻毒潜在反应的生物学理解。

结果

我们总共鉴定出22个q值<0.1的单核苷酸多态性(SNP),分布在五条染色体上。高度显著的SNP与体重增加(5号染色体上3个SNP、1号染色体上1个SNP和3号染色体上1个SNP)、在465 - 510 nm波长范围内以光密度测量的血浆颜色(10个SNP且均在10号染色体上)以及血浆中β2 -球蛋白的百分比(1号染色体上15个SNP和2号染色体上1个SNP)相关。与代谢过程、细胞增殖和主要先天性免疫过程相关的生物学途径是最常显著富集的生物学途径。此外,基于网络的分析产生了两个高可信度网络,一个以大肿瘤抑制激酶1(LATS1)和2(LATS)为中心,另一个涉及肌球蛋白重链6(MYH6)。

结论

我们鉴定出了几个与肉鸡对巨型艾美耳球虫反应中所测性状相关的强候选基因和基因组区域。此外,GWAS后功能分析表明,参与组织增殖和修复以及主要先天性免疫反应的生物学途径和网络可能在肉鸡感染巨型艾美耳球虫的早期阶段发挥最重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271d/4659166/6ee7cf30706b/12711_2015_170_Fig1_HTML.jpg

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