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使用整合全基因组关联研究结果的单步基因组最佳线性无偏预测模型提高基因组预测准确性。

Enhancing Genomic Prediction Accuracy with a Single-Step Genomic Best Linear Unbiased Prediction Model Integrating Genome-Wide Association Study Results.

作者信息

Pang Zhixu, Wang Wannian, Huang Pu, Zhang Hongzhi, Zhang Siying, Yang Pengkun, Qiao Liying, Liu Jianhua, Pan Yangyang, Yang Kaijie, Liu Wenzhong

机构信息

College of Animal Science, Shanxi Agricultural University, Taigu, Jinzhong 030801, China.

出版信息

Animals (Basel). 2025 Apr 29;15(9):1268. doi: 10.3390/ani15091268.

DOI:10.3390/ani15091268
PMID:40362083
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12070965/
Abstract

Genomic selection (GS) is a genetic breeding method that uses genome-wide marker information to improve the accuracy of the prediction of complex traits. The single-step GBLUP (ssGBLUP) model, which integrates pedigree, phenotypic, and genomic data, has improved genomic prediction. However, ssGBLUP assumes that all markers contribute equally to genetic variance, which can limit its predictive accuracy, especially for traits controlled by major genes. To overcome this limitation, we integrate results from genome-wide association studies (GWAS) into an enhanced ssGBLUP framework, termed single-step genome-wide association assisted BLUP (ssGWABLUP). Our approach assigns differential weights to markers on the basis of their GWAS results, thereby increasing the contribution of effective markers while diminishing the influence of ineffective ones during the construction of the genomic relationship matrix. By incorporating pseudo quantitative trait nucleotides (pQTNs) as covariates, we aim to capture the effects of markers closely associated with major causal variants, leading to the development of the ssGWABLUP_pQTNs. Compared with weighted ssGBLUP (WssGBLUP), the ssGWABLUP model demonstrated superior accuracy and dispersion across different genetic architectures. We then compared the performance of our proposed ssGWABLUP_pQTNs model against both ssGBLUP and ssGWABLUP across various genetic scenarios. Our results demonstrate that ssGWABLUP_pQTNs outperforms other models in terms of prediction accuracy, particularly in scenarios with simpler genetic architectures. Additionally, evaluation using pig dataset confirmed the effectiveness of ssGWABLUP_pQTNs, highlighting its potential for practical breeding applications. The incorporation of pQTNs and a weighted genomic relationship matrix presents a promising and potentially scalable approach to further enhance genomic prediction, with potential implications for improving the accuracy of genomic selection in breeding programs.

摘要

基因组选择(GS)是一种遗传育种方法,它利用全基因组标记信息来提高复杂性状预测的准确性。单步GBLUP(ssGBLUP)模型整合了系谱、表型和基因组数据,改进了基因组预测。然而,ssGBLUP假定所有标记对遗传方差的贡献相同,这可能会限制其预测准确性,特别是对于由主基因控制的性状。为克服这一限制,我们将全基因组关联研究(GWAS)的结果整合到一个增强的ssGBLUP框架中,称为单步全基因组关联辅助BLUP(ssGWABLUP)。我们的方法根据标记的GWAS结果为其分配不同的权重,从而在构建基因组关系矩阵时增加有效标记的贡献,同时减少无效标记的影响。通过纳入伪数量性状核苷酸(pQTNs)作为协变量,我们旨在捕捉与主要因果变异密切相关的标记的效应,从而开发出ssGWABLUP_pQTNs。与加权ssGBLUP(WssGBLUP)相比,ssGWABLUP模型在不同遗传结构上表现出更高的准确性和离散度。然后,我们在各种遗传场景下比较了我们提出的ssGWABLUP_pQTNs模型与ssGBLUP和ssGWABLUP的性能。我们的结果表明,ssGWABLUP_pQTNs在预测准确性方面优于其他模型,特别是在遗传结构较简单的场景中。此外,使用猪数据集进行的评估证实了ssGWABLUP_pQTNs的有效性,突出了其在实际育种应用中的潜力。纳入pQTNs和加权基因组关系矩阵为进一步提高基因组预测提供了一种有前景且可能可扩展的方法,对提高育种计划中基因组选择的准确性具有潜在意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb4f/12070965/b7d25a0ef0ab/animals-15-01268-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb4f/12070965/9848545932aa/animals-15-01268-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb4f/12070965/d135ec046d99/animals-15-01268-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb4f/12070965/b7d25a0ef0ab/animals-15-01268-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb4f/12070965/9848545932aa/animals-15-01268-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb4f/12070965/d135ec046d99/animals-15-01268-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb4f/12070965/b7d25a0ef0ab/animals-15-01268-g003.jpg

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本文引用的文献

1
GWABLUP: genome-wide association assisted best linear unbiased prediction of genetic values.GWABLUP:基于全基因组关联的最佳线性无偏遗传预测。
Genet Sel Evol. 2024 Mar 1;56(1):17. doi: 10.1186/s12711-024-00881-y.
2
Genome-wide scans identify biological and metabolic pathways regulating carcass and meat quality traits in beef cattle.全基因组扫描鉴定调控肉牛胴体和肉质性状的生物和代谢途径。
Meat Sci. 2024 Mar;209:109402. doi: 10.1016/j.meatsci.2023.109402. Epub 2023 Dec 1.
3
Alternative SNP weighting for multi-step and single-step genomic BLUP in the presence of causative variants.
在存在因果变异的情况下,多步和单步基因组最佳线性无偏预测中的替代单核苷酸多态性加权
J Anim Breed Genet. 2023 Nov;140(6):679-694. doi: 10.1111/jbg.12817. Epub 2023 Aug 7.
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SLEMM: million-scale genomic predictions with window-based SNP weighting.SLEMM:基于窗口的 SNP 加权的大规模基因组预测。
Bioinformatics. 2023 Mar 1;39(3). doi: 10.1093/bioinformatics/btad127.
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Longitudinal genome-wide association studies of milk production traits in Holstein cattle using whole-genome sequence data imputed from medium-density chip data.利用中密度芯片数据推断的全基因组序列数据对荷斯坦奶牛产奶性状进行的纵向全基因组关联研究。
J Dairy Sci. 2023 Apr;106(4):2535-2550. doi: 10.3168/jds.2022-22277. Epub 2023 Feb 14.
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BayesR3 enables fast MCMC blocked processing for largescale multi-trait genomic prediction and QTN mapping analysis.贝叶斯 R3 能够实现大规模多性状基因组预测和 QTN 映射分析的快速 MCMC 块处理。
Commun Biol. 2022 Jul 5;5(1):661. doi: 10.1038/s42003-022-03624-1.
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Efficient weighting methods for genomic best linear-unbiased prediction (BLUP) adapted to the genetic architectures of quantitative traits.高效的基因组最佳线性无偏预测(BLUP)加权方法,适用于数量性状的遗传结构。
Heredity (Edinb). 2021 Feb;126(2):320-334. doi: 10.1038/s41437-020-00372-y. Epub 2020 Sep 26.
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Single-Step Genomic Evaluations from Theory to Practice: Using SNP Chips and Sequence Data in BLUPF90.从理论到实践的单步基因组评估:在 BLUPF90 中使用 SNP 芯片和序列数据。
Genes (Basel). 2020 Jul 14;11(7):790. doi: 10.3390/genes11070790.
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KAML: improving genomic prediction accuracy of complex traits using machine learning determined parameters.KAML:使用机器学习确定的参数来提高复杂性状的基因组预测准确性。
Genome Biol. 2020 Jun 17;21(1):146. doi: 10.1186/s13059-020-02052-w.
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