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拷贝数变异和全基因组关联分析揭示了与肉牛饲料转化率相关的潜在基因和代谢途径。

Copy number variations and genome-wide associations reveal putative genes and metabolic pathways involved with the feed conversion ratio in beef cattle.

作者信息

de Almeida Santana Miguel Henrique, Junior Gerson Antônio Oliveira, Cesar Aline Silva Mello, Freua Mateus Castelani, da Costa Gomes Rodrigo, da Luz E Silva Saulo, Leme Paulo Roberto, Fukumasu Heidge, Carvalho Minos Esperândio, Ventura Ricardo Vieira, Coutinho Luiz Lehmann, Kadarmideen Haja N, Ferraz José Bento Sterman

机构信息

Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 7, 1870, Frederiksberg, Denmark.

Faculdade de Zootecnia e Engenharia de Alimentos, University of São Paulo, Duque de Caxias Norte, 225, 13635-900, Pirassununga, Brazil.

出版信息

J Appl Genet. 2016 Nov;57(4):495-504. doi: 10.1007/s13353-016-0344-7. Epub 2016 Mar 21.

Abstract

The use of genome-wide association results combined with other genomic approaches may uncover genes and metabolic pathways related to complex traits. In this study, the phenotypic and genotypic data of 1475 Nellore (Bos indicus) cattle and 941,033 single nucleotide polymorphisms (SNPs) were used for genome-wide association study (GWAS) and copy number variations (CNVs) analysis in order to identify candidate genes and putative pathways involved with the feed conversion ratio (FCR). The GWAS was based on the Bayes B approach analyzing genomic windows with multiple regression models to estimate the proportion of genetic variance explained by each window. The CNVs were detected with PennCNV software using the log R ratio and B allele frequency data. CNV regions (CNVRs) were identified with CNVRuler and a linear regression was used to associate CNVRs and the FCR. Functional annotation of associated genomic regions was performed with the Database for Annotation, Visualization and Integrated Discovery (DAVID) and the metabolic pathways were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG). We showed five genomic windows distributed over chromosomes 4, 6, 7, 8, and 24 that explain 12 % of the total genetic variance for FCR, and detected 12 CNVRs (chromosomes 1, 5, 7, 10, and 12) significantly associated [false discovery rate (FDR) < 0.05] with the FCR. Significant genomic regions (GWAS and CNV) harbor candidate genes involved in pathways related to energetic, lipid, and protein metabolism. The metabolic pathways found in this study are related to processes directly connected to feed efficiency in beef cattle. It was observed that, even though different genomic regions and genes were found between the two approaches (GWAS and CNV), the metabolic processes covered were related to each other. Therefore, a combination of the approaches complement each other and lead to a better understanding of the FCR.

摘要

将全基因组关联研究结果与其他基因组方法相结合,可能会揭示与复杂性状相关的基因和代谢途径。在本研究中,利用1475头Nellore(印度瘤牛)的表型和基因型数据以及941,033个单核苷酸多态性(SNP)进行全基因组关联研究(GWAS)和拷贝数变异(CNV)分析,以确定与饲料转化率(FCR)相关的候选基因和假定途径。GWAS基于贝叶斯B方法,使用多元回归模型分析基因组窗口,以估计每个窗口解释的遗传方差比例。使用PennCNV软件,利用对数R比率和B等位基因频率数据检测CNV。使用CNVRuler识别CNV区域(CNVR),并使用线性回归将CNVR与FCR相关联。使用注释、可视化和综合发现数据库(DAVID)对相关基因组区域进行功能注释,并从京都基因与基因组百科全书(KEGG)获得代谢途径。我们发现分布在4号、6号、7号、8号和24号染色体上的5个基因组窗口解释了FCR总遗传方差的12%,并检测到12个CNVR(1号、5号、7号、10号和12号染色体)与FCR显著相关[错误发现率(FDR)<0.05]。显著的基因组区域(GWAS和CNV)包含参与能量、脂质和蛋白质代谢相关途径的候选基因。本研究中发现的代谢途径与肉牛饲料效率直接相关的过程有关。据观察,尽管在两种方法(GWAS和CNV)之间发现了不同的基因组区域和基因,但所涵盖的代谢过程相互关联。因此,两种方法相互补充,有助于更好地理解FCR。

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