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杂交肉牛血浆代谢物的基因组遗传力和全基因组关联研究

Genomic Heritability and Genome-Wide Association Studies of Plasma Metabolites in Crossbred Beef Cattle.

作者信息

Li Jiyuan, Akanno Everestus C, Valente Tiago S, Abo-Ismail Mohammed, Karisa Brian K, Wang Zhiquan, Plastow Graham S

机构信息

Livestock Gentec, Department of Agriculture, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, AB, Canada.

Department of Animal Science, Ethology and Animal Ecology Research Group, São Paulo State University, Jaboticabal, Brazil.

出版信息

Front Genet. 2020 Sep 24;11:538600. doi: 10.3389/fgene.2020.538600. eCollection 2020.

Abstract

Metabolites, substrates or products of metabolic processes, are involved in many biological functions, such as energy metabolism, signaling, stimulatory and inhibitory effects on enzymes and immunological defense. Metabolomic phenotypes are influenced by combination of genetic and environmental effects allowing for metabolome-genome-wide association studies (mGWAS) as a powerful tool to investigate the relationship between these phenotypes and genetic variants. The objectives of this study were to estimate genomic heritability and perform mGWAS and functional enrichment analyses for a set of plasma metabolites in Canadian crossbred beef cattle. Thirty-three plasma metabolites and 45,266 single nucleotide polymorphisms (SNPs) were available for 475 animals. Genomic heritability for all metabolites was estimated using genomic best linear unbiased prediction (GBLUP) including genomic breed composition as covariates in the model. A single-step GBLUP implemented in BLUPF90 programs was used to determine SNP values and the proportion of genetic variance explained by SNP windows containing 10 consecutive SNPs. The top 10 SNP windows that explained the largest genetic variation for each metabolite were identified and mapped to detect corresponding candidate genes. Functional enrichment analyses were performed on metabolites and their candidate genes using the Ingenuity Pathway Analysis software. Eleven metabolites showed low to moderate heritability that ranged from 0.09 ± 0.15 to 0.36 ± 0.15, while heritability estimates for 22 metabolites were zero or negligible. This result indicates that while variations in 11 metabolites were due to genetic variants, the majority are largely influenced by environment. Three significant SNP associations were detected for betaine (rs109862186), L-alanine (rs81117935), and L-lactic acid (rs42009425) based on Bonferroni correction for multiple testing (family wise error rate <0.05). The SNP rs81117935 was found to be located within the gene () showing a possible association with the regulation of L-alanine concentration. Other candidate genes were identified based on additive genetic variance explained by SNP windows of 10 consecutive SNPs. The observed heritability estimates and the candidate genes and networks identified in this study will serve as baseline information for research into the utilization of plasma metabolites for genetic improvement of crossbred beef cattle.

摘要

代谢物,即代谢过程的底物或产物,参与许多生物学功能,如能量代谢、信号传导、对酶的刺激和抑制作用以及免疫防御。代谢组学表型受遗传和环境效应组合的影响,这使得代谢组-全基因组关联研究(mGWAS)成为研究这些表型与遗传变异之间关系的有力工具。本研究的目的是估计加拿大杂交肉牛一组血浆代谢物的基因组遗传力,并进行mGWAS和功能富集分析。对475头动物可获得33种血浆代谢物和45,266个单核苷酸多态性(SNP)。使用基因组最佳线性无偏预测(GBLUP)估计所有代谢物的基因组遗传力,模型中包括基因组品种组成作为协变量。在BLUPF90程序中实施的单步GBLUP用于确定SNP值以及由包含10个连续SNP的SNP窗口解释的遗传方差比例。确定并定位了每个代谢物解释最大遗传变异的前10个SNP窗口,以检测相应的候选基因。使用Ingenuity Pathway Analysis软件对代谢物及其候选基因进行功能富集分析。11种代谢物显示出低到中等的遗传力,范围从0.09±0.15到0.36±0.15,而22种代谢物的遗传力估计值为零或可忽略不计。这一结果表明,虽然11种代谢物的变异是由于遗传变异,但大多数主要受环境影响。基于多重检验的Bonferroni校正(家族性错误率<0.05),检测到甜菜碱(rs109862186)、L-丙氨酸(rs81117935)和L-乳酸(rs42009425)的三个显著SNP关联。发现SNP rs81117935位于基因()内,显示出与L-丙氨酸浓度调节的可能关联。基于由10个连续SNP的SNP窗口解释的加性遗传方差鉴定了其他候选基因。本研究中观察到的遗传力估计值以及鉴定的候选基因和网络将作为利用血浆代谢物进行杂交肉牛遗传改良研究的基线信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/326f/7542097/6b183441b77a/fgene-11-538600-g001.jpg

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