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A computationally efficient algorithm to leverage average information REML for (co)variance component estimation in the genomic era 在基因组时代利用平均信息 REML 进行(共)方差成分估计的高效计算算法
IF 4.1 1区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2024-11-21 DOI: 10.1186/s12711-024-00939-x
Ismo Strandén, Esa A. Mäntysaari, Martin H. Lidauer, Robin Thompson, Hongding Gao
Methods for estimating variance components (VC) using restricted maximum likelihood (REML) typically require elements from the inverse of the coefficient matrix of the mixed model equations (MME). As genomic information becomes more prevalent, the coefficient matrix of the MME becomes denser, presenting a challenge for analyzing large datasets. Thus, computational algorithms based on iterative solving and Monte Carlo approximation of the inverse of the coefficient matrix become appealing. While the standard average information REML (AI-REML) is known for its rapid convergence, its computational intensity imposes limitations. In particular, the standard AI-REML requires solving the MME for each VC, which can be computationally demanding, especially when dealing with complex models with many VC. To bridge this gap, here we (1) present a computationally efficient and tractable algorithm, named the augmented AI-REML, which facilitates the AI-REML by solving an augmented MME only once within each REML iteration; and (2) implement this approach for VC estimation in a general framework of a multi-trait GBLUP model. VC estimation was investigated based on the number of VC in the model, including a two-trait, three-trait, four-trait, and five-trait GBLUP model. We compared the augmented AI-REML with the standard AI-REML in terms of computing time per REML iteration. Direct and iterative solving methods were used to assess the advances of the augmented AI-REML. When using the direct solving method, the augmented AI-REML and the standard AI-REML required similar computing times for models with a small number of VC (the two- and three-trait GBLUP model), while the augmented AI-REML demonstrated more notable reductions in computing time as the number of VC in the model increased. When using the iterative solving method, the augmented AI-REML demonstrated substantial improvements in computational efficiency compared to the standard AI-REML. The elapsed time of each REML iteration was reduced by 75%, 84%, and 86% for the two-, three-, and four-trait GBLUP models, respectively. The augmented AI-REML can considerably reduce the computing time within each REML iteration, particularly when using an iterative solver. Our results demonstrate the potential of the augmented AI-REML as an appealing approach for large-scale VC estimation in the genomic era.
使用限制性最大似然法(REML)估计方差成分(VC)的方法通常需要混合模型方程(MME)系数矩阵逆矩阵中的元素。随着基因组信息越来越普遍,MME 的系数矩阵也变得越来越密集,这给分析大型数据集带来了挑战。因此,基于系数矩阵逆的迭代求解和蒙特卡罗近似的计算算法变得非常有吸引力。虽然标准平均信息 REML(AI-REML)以收敛速度快而著称,但其计算强度也有局限性。特别是,标准平均信息 REML 需要求解每个 VC 的 MME,这对计算能力要求很高,尤其是在处理有许多 VC 的复杂模型时。为了弥补这一差距,我们在这里(1)提出了一种计算效率高、易于操作的算法,命名为增强型 AI-REML,该算法在每次 REML 迭代中只需求解一次增强型 MME,从而简化了 AI-REML;(2)在多性状 GBLUP 模型的一般框架下,将这种方法用于 VC 估计。我们根据模型中 VC 的数量对 VC 估计进行了研究,包括二性状、三性状、四性状和五性状 GBLUP 模型。我们比较了增强型 AI-REML 和标准 AI-REML 每次 REML 迭代的计算时间。我们使用了直接求解法和迭代求解法来评估增强型 AI-REML 的进步。在使用直接求解法时,增强型 AI-REML 和标准 AI-REML 对具有少量 VC 的模型(两特征和三特征 GBLUP 模型)所需的计算时间相似,而随着模型中 VC 数量的增加,增强型 AI-REML 的计算时间明显减少。在使用迭代求解方法时,增强型 AI-REML 的计算效率比标准 AI-REML 有了大幅提高。对于两特征、三特征和四特征 GBLUP 模型,每次 REML 迭代所需的时间分别减少了 75%、84% 和 86%。增强型 AI-REML 可以大大减少每次 REML 迭代的计算时间,尤其是在使用迭代求解器时。我们的研究结果证明了增强型 AI-REML 作为基因组时代大规模 VC 估计的一种有吸引力的方法的潜力。
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引用次数: 0
On the ability of the LR method to detect bias when there is pedigree misspecification and lack of connectedness 关于在血统指定错误和缺乏关联性的情况下 LR 方法检测偏差的能力
IF 4.1 1区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2024-11-21 DOI: 10.1186/s12711-024-00943-1
Alan M. Pardo, Andres Legarra, Zulma G. Vitezica, Natalia S. Forneris, Daniel O. Maizon, Sebastián Munilla
Cross-validation techniques in genetic evaluations encounter limitations due to the unobservable nature of breeding values and the challenge of validating estimated breeding values (EBVs) against pre-corrected phenotypes, challenges which the Linear Regression (LR) method addresses as an alternative. Furthermore, beef cattle genetic evaluation programs confront challenges with connectedness among herds and pedigree errors. The objective of this work was to evaluate the LR method's performance under pedigree errors and weak connectedness typical in beef cattle genetic evaluations, through simulation. We simulated a beef cattle population resembling the Argentinean Brangus, including a quantitative trait selected over six pseudo-generations with a heritability of 0.4. This study considered various scenarios, including: 25% and 40% pedigree errors (PE-25 and PE-40), weak and strong connectedness among herds (WCO and SCO, respectively), and a benchmark scenario (BEN) with complete pedigree and optimal herd connections. Over six pseudo-generations of selection, genetic gain was simulated to be under- and over-estimated in PE-40 and WCO, respectively, contrary to the BEN scenario which was unbiased. In genetic evaluations with PE-25 and PE-40, true biases of − 0.13 and − 0.18 genetic standard deviations were simulated, respectively. In the BEN scenario, the LR method accurately estimated bias, however, in PE-25 and PE-40 scenarios, it overestimated biases by 0.17 and 0.25 genetic standard deviations, respectively. In herds facing WCO, significant true bias due to confounding environmental and genetic effects was simulated, and the corresponding LR statistic failed to accurately estimate the magnitude and direction of this bias. On average, true dispersion values were close to one for BEN, PE-40, SCO and WCO, showing no significant inflation or deflation, and the values were accurately estimated by LR. However, PE-25 exhibited inflation of EBVs and was slightly underestimated by LR. Accuracies and reliabilities showed good agreement between true and LR estimated values for the scenarios evaluated. The LR method demonstrated limitations in identifying biases induced by incomplete pedigrees, including scenarios with as much as 40% pedigree errors, or lack of connectedness, but it was effective in assessing dispersion, and population accuracies and reliabilities even in the challenging scenarios addressed.
由于育种值的不可观测性和根据预校正表型验证估计育种值(EBV)的挑战,遗传评估中的交叉验证技术遇到了限制,而线性回归(LR)方法可作为一种替代方法来应对这些挑战。此外,肉牛遗传评估项目还面临着牛群之间的关联性和血统误差的挑战。这项工作的目的是通过模拟,评估线性回归法在肉牛遗传评估中典型的血统误差和弱联系情况下的性能。我们模拟了一个与阿根廷布兰格斯牛相似的肉牛种群,包括一个在六个假世代中选择的遗传率为 0.4 的数量性状。这项研究考虑了各种情况,包括25% 和 40% 的血统误差(PE-25 和 PE-40)、牛群之间的弱联系和强联系(分别为 WCO 和 SCO),以及具有完整血统和最佳牛群联系的基准方案(BEN)。在六个假世代的选择过程中,PE-40 和 WCO 模拟的遗传增益分别被低估和高估,而 BEN 情景则没有偏差。在 PE-25 和 PE-40 的遗传评估中,模拟的真实偏差分别为-0.13 和-0.18 个遗传标准差。在 BEN 情景中,LR 方法准确估计了偏差,但在 PE-25 和 PE-40 情景中,它分别高估了 0.17 和 0.25 个遗传标准差。在面临 WCO 的牛群中,模拟了由于环境和遗传效应的混杂而导致的显著真实偏差,而相应的 LR 统计量未能准确估计这种偏差的大小和方向。平均而言,BEN、PE-40、SCO 和 WCO 的真实离散值接近于 1,没有出现明显的膨胀或缩小,LR 统计量也能准确估计出这些值。然而,PE-25 的 EBV 值出现了膨胀,LR 估算值略微偏低。在所评估的方案中,真实值和 LR 估计值之间的准确度和可靠性显示出良好的一致性。LR 方法在识别不完整血统(包括血统误差高达 40% 或缺乏关联性的情况)引起的偏差方面存在局限性,但它在评估分散性、种群准确性和可靠性方面非常有效,即使是在具有挑战性的情况下也是如此。
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引用次数: 0
Empirical versus estimated accuracy of imputation: optimising filtering thresholds for sequence imputation 归因的经验准确性与估计准确性:优化序列归因的过滤阈值
IF 4.1 1区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2024-11-15 DOI: 10.1186/s12711-024-00942-2
Tuan V. Nguyen, Sunduimijid Bolormaa, Coralie M. Reich, Amanda J. Chamberlain, Christy J. Vander Jagt, Hans D. Daetwyler, Iona M. MacLeod
Genotype imputation is a cost-effective method for obtaining sequence genotypes for downstream analyses such as genome-wide association studies (GWAS). However, low imputation accuracy can increase the risk of false positives, so it is important to pre-filter data or at least assess the potential limitations due to imputation accuracy. In this study, we benchmarked three different imputation programs (Beagle 5.2, Minimac4 and IMPUTE5) and compared the empirical accuracy of imputation with the software estimated accuracy of imputation (Rsqsoft). We also tested the accuracy of imputation in cattle for autosomal and X chromosomes, SNP and INDEL, when imputing from either low-density or high-density genotypes. The accuracy of imputing sequence variants from real high-density genotypes was higher than from low-density genotypes. In our software benchmark, all programs performed well with only minor differences in accuracy. While there was a close relationship between empirical imputation accuracy and the imputation Rsqsoft, this differed considerably for Minimac4 compared to Beagle 5.2 and IMPUTE5. We found that the Rsqsoft threshold for removing poorly imputed variants must be customised according to the software and this should be accounted for when merging data from multiple studies, such as in meta-GWAS studies. We also found that imposing an Rsqsoft filter has a positive impact on genomic regions with poor imputation accuracy due to large segmental duplications that are susceptible to error-prone alignment. Overall, our results showed that on average the imputation accuracy for INDEL was approximately 6% lower than SNP for all software programs. Importantly, the imputation accuracy for the non-PAR (non-Pseudo-Autosomal Region) of the X chromosome was comparable to autosomal imputation accuracy, while for the PAR it was substantially lower, particularly when starting from low-density genotypes. This study provides an empirically derived approach to apply customised software-specific Rsqsoft thresholds for downstream analyses of imputed variants, such as needed for a meta-GWAS. The very poor empirical imputation accuracy for variants on the PAR when starting from low density genotypes demonstrates that this region should be imputed starting from a higher density of real genotypes.
基因型估算是为全基因组关联研究(GWAS)等下游分析获取序列基因型的一种经济有效的方法。然而,低估算准确性会增加假阳性的风险,因此预先过滤数据或至少评估估算准确性可能带来的限制是非常重要的。在本研究中,我们对三种不同的估算程序(Beagle 5.2、Minimac4 和 IMPUTE5)进行了基准测试,并比较了估算的经验准确性和软件估算的估算准确性(Rsqsoft)。我们还测试了牛的常染色体和 X 染色体、SNP 和 INDEL 在从低密度或高密度基因型推算时的推算准确性。从真实的高密度基因型推算序列变异的准确率高于从低密度基因型推算的准确率。在我们的软件基准测试中,所有程序都表现良好,只是在准确性上略有不同。虽然经验估算准确率与估算 Rsqsoft 之间关系密切,但 Minimac4 与 Beagle 5.2 和 IMPUTE5 相比差别很大。我们发现,剔除归因不佳变异的 Rsqsoft 阈值必须根据软件进行定制,在合并来自多个研究的数据时(如在 meta-GWAS 研究中)应考虑到这一点。我们还发现,实施 Rsqsoft 过滤器对估算准确性较差的基因组区域有积极影响,因为这些区域存在大的片段重复,容易发生配对错误。总之,我们的结果显示,在所有软件程序中,INDEL 的估算准确率平均比 SNP 低约 6%。重要的是,X 染色体非 PAR(非假常染色体区域)的估算准确率与常染色体估算准确率相当,而 PAR 的估算准确率则要低得多,尤其是从低密度基因型开始估算时。本研究提供了一种根据经验得出的方法,可将定制软件特定的 Rsqsoft 阈值应用于推算变异的下游分析,如元全球基因组分析系统(meta-GWAS)所需的分析。当从低密度基因型开始计算时,PAR 上变异的经验估算准确率非常低,这表明该区域应从更高密度的真实基因型开始估算。
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引用次数: 0
The effect of phenotyping, adult selection, and mating strategies on genetic gain and rate of inbreeding in black soldier fly breeding programs 表型、成蝇选择和交配策略对黑实蝇育种项目遗传增益和近交率的影响
IF 4.1 1区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2024-11-04 DOI: 10.1186/s12711-024-00938-y
Margot Slagboom, Hanne Marie Nielsen, Morten Kargo, Mark Henryon, Laura Skrubbeltrang Hansen
The aim of this study was to compare genetic gain and rate of inbreeding for different mass selection breeding programs with the aim of increasing larval body weight (LBW) in black soldier flies. The breeding programs differed in: (1) sampling of individuals for phenotyping (either random over the whole population or a fixed number per full sib family), (2) selection of adult flies for breeding (based on an adult individual’s phenotype for LBW or random from larvae preselected based on LBW), and (3) mating strategy (mating in a group with unequal male contributions or controlled between two females and one male). In addition, the numbers of phenotyped and preselected larvae were varied. The sex of an individual was unknown during preselection and females had higher LBW, resulting in more females being preselected. Selecting adult flies based on their phenotype for LBW increased genetic gain by 0.06 genetic standard deviation units compared to randomly selecting from the preselected larvae. Fixing the number of phenotyped larvae per family increased the rate of inbreeding by 0.15 to 0.20% per generation. Controlled mating compared to group mating decreased the rate of inbreeding by 0.02 to 0.03% per generation. Phenotyping more than 4000 larvae resulted in a lack of preselected males due to the sexual dimorphism. Preselecting both too few and too many larvae could negatively impact genetic gain, depending on the breeding program. A mass selection breeding programs in which the adult fly is selected based on their larval phenotype, breeding animals mate in a group and sampling larvae for phenotyping at random over the whole population is recommended for black soldier flies, considering the positive effect on rates of genetic gain and inbreeding. The number of phenotyped and preselected larvae should be calculated based on the expected female weight deviation to ensure sufficient male and female candidates are selected.
本研究旨在比较不同大规模选育计划的遗传增益和近交率,目的是提高黑兵蝇幼虫体重(LBW)。育种方案在以下方面有所不同(1)表型个体取样(在整个种群中随机取样或在每个兄弟姐妹家族中固定取样),(2)选择成蝇进行繁殖(根据成蝇个体的低体重表型或从根据低体重预选的幼虫中随机选择),(3)交配策略(在雄性贡献不均的群体中交配或在两只雌蝇和一只雄蝇之间控制交配)。此外,表型幼虫和预选幼虫的数量也各不相同。在预选过程中,个体的性别是未知的,而雌蝇的低体重率较高,因此更多的雌蝇被预选。与从预选幼虫中随机选择相比,根据表型选择成蝇的枸杞体重增加了 0.06 个遗传标准差单位。固定每个家系的表型幼虫数量可使近交率每代提高 0.15% 至 0.20%。控制交配与群体交配相比,每代近交率降低了 0.02% 至 0.03%。对 4000 多条幼虫进行表型分析后发现,由于性二型,缺乏预选雄虫。预选幼虫数量过少或过多都会对遗传增益产生负面影响,这取决于育种计划。考虑到对遗传增殖率和近交率的积极影响,建议对黑兵蝇实施大规模选择育种计划,即根据幼虫表型选择成蝇,育种动物在群体中交配,并在整个种群中随机抽取幼虫进行表型分析。应根据预期的雌蝇体重偏差计算表型和预选幼虫的数量,以确保选出足够的雌雄候选幼虫。
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引用次数: 0
Investigating genotype by environment interaction for beef cattle fertility traits in commercial herds in northern Australia with multi-trait analysis 通过多性状分析调查澳大利亚北部商业牛群中肉牛繁殖力性状的基因型与环境的交互作用
IF 4.1 1区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2024-10-31 DOI: 10.1186/s12711-024-00936-0
James P. Copley, Benjamin J. Hayes, Elizabeth M. Ross, Shannon Speight, Geoffry Fordyce, Benjamin J. Wood, Bailey N. Engle
Genotype by environment interactions (GxE) affect a range of production traits in beef cattle. Quantifying the effect of GxE in commercial and multi-breed herds is challenging due to unknown genetic linkage between animals across environment levels. The primary aim of this study was to use multi-trait models to investigate GxE for three heifer fertility traits, corpus luteum (CL) presence, first pregnancy and second pregnancy, in a large tropical beef multibreed dataset (n = 21,037). Environmental levels were defined by two different descriptors, burden of heat load (temperature humidity index, THI) and nutritional availability (based on mean average daily gain for the herd, ADWG). To separate the effects of genetic linkage and real GxE across the environments, 1000 replicates of a simulated phenotype were generated by simulating QTL effects with no GxE onto real marker genotypes from the population, to determine the genetic correlations that could be expected across environments due to the existing genetic linkage only. Correlations from the real phenotypes were then compared to the empirical distribution under the null hypothesis from the simulated data. By adopting this approach, this study attempted to establish if low genetic correlations between environmental levels were due to GxE or insufficient genetic linkage between animals in each environmental level. The correlations (being less than <0.8) for the real phenotypes were indicative of GxE for CL presence between ADWG environmental levels and in pregnancy traits. However, none of the correlations for CL presence or first pregnancy between ADWG levels were below the 5th percentile value for the empirical distribution under the null hypothesis from the simulated data. Only one statistically significant (P < 0.05) indication of GxE for first pregnancy was found between THI environmental levels, where rg = 0.28 and 5th percentile value = 0.29, and this result was marginal. Only one case of statistically significant GxE for fertility traits was detected for first pregnancy between THI environmental levels 2 and 3. Other initial indications of GxE that were observed from the real phenotypes did not prove significant when compared to an empirical null distribution from simulated phenotypes. The lack of compelling evidence of GxE indicates that direct selection for fertility traits can be made accurately, using a single evaluation, regardless of environment.
基因型与环境的相互作用(GxE)会影响肉牛的一系列生产性状。由于不同环境水平下动物之间的遗传联系未知,因此量化 GxE 对商业牛群和多品种牛群的影响具有挑战性。本研究的主要目的是在一个大型热带肉牛多品种数据集(n = 21,037)中,使用多性状模型研究 GxE 对黄体(CL)存在、首次妊娠和第二次妊娠这三个母牛繁殖性状的影响。环境水平由两个不同的描述因子定义,即热负荷(温度湿度指数,THI)和营养供应(基于牛群平均日增重,ADWG)。为了区分遗传连锁和真实 GxE 在不同环境中的影响,通过将无 GxE 的 QTL 效应模拟到种群的真实标记基因型上,生成了 1000 个重复的模拟表型,以确定仅由于现有的遗传连锁而可能在不同环境中产生的遗传相关性。然后将真实表型的相关性与模拟数据零假设下的经验分布进行比较。通过采用这种方法,本研究试图确定环境水平之间的低遗传相关性是由于 GxE 还是由于各环境水平中动物之间的遗传联系不足。实际表型的相关性(小于<0.8)表明,ADWG 环境水平与妊娠性状之间的 CL 存在 GxE。然而,在模拟数据的零假设下,ADWG 水平与 CL 存在或首次怀孕之间的相关性均不低于经验分布的第 5 百分位值。在 THI 环境水平之间只发现了一个具有统计学意义(P < 0.05)的 GxE 显示,即 rg = 0.28 和第 5 百分位值 = 0.29,而且这个结果是边缘性的。在 THI 环境水平 2 和 3 之间,仅发现一例具有统计学意义的初孕生殖力性状 GxE。从实际表型中观察到的其他 GxE 初步迹象与模拟表型的经验零分布相比并不显著。缺乏令人信服的 GxE 证据表明,无论环境如何,都可以通过单一评价对育种性状进行准确的直接选择。
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引用次数: 0
Combined genomic evaluation of Merino and Dohne Merino Australian sheep populations 美利奴羊和多恩美利奴羊澳大利亚种群的联合基因组评估
IF 4.1 1区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2024-09-30 DOI: 10.1186/s12711-024-00934-2
Marine Wicki, Daniel J. Brown, Phillip M. Gurman, Jérôme Raoul, Andrés Legarra, Andrew A. Swan
The Dohne Merino sheep was introduced to Australia from South Africa in the 1990s. It was primarily used in crosses with the Merino breed sheep to improve on attributes such as reproduction and carcass composition. Since then, this breed has continued to expand in Australia but the number of genotyped and phenotyped purebred individuals remains low, calling into question the accuracy of genomic selection. The Australian Merino, on the other hand, has a substantial reference population in a separate genomic evaluation (MERINOSELECT). Combining these resources could fast track the impact of genomic selection on the smaller breed, but the efficacy of this needs to be investigated. This study was based on a dataset of 53,663 genotypes and more than 2 million phenotypes. Its main objectives were (1) to characterize the genetic structure of Merino and Dohne Merino breeds, (2) to investigate the utility of combining their evaluations in terms of quality of predictions, and (3) to compare several methods of genetic grouping. We used the ‘LR-method’ (Linear Regression) for these assessments. We found very low Fst values (below 0.048) between the different Merino lines and Dohne breed considered in our study, indicating very low genetic differentiation. Principal component analysis revealed three distinct groups, identified as purebred Merino, purebred Dohne, and crossbred animals. Considering the whole population in the reference led to the best quality of predictions and the largest increase in accuracy (from ‘LR-method’) from pedigree to genomic-based evaluations: 0.18, 0.14 and 0.16 for yearling fibre diameter (YFD), yearling greasy fleece weight (YGFW) and yearling liveweight (YWT), respectively. Combined genomic evaluations showed higher accuracies than the evaluation based on the Dohne reference only (accuracies increased by 0.16, 0.06 and 0.07 for YFD, YGFW, and YWT, respectively). For the combined genomic evaluations, metafounder models were more accurate than Unknown Parent Groups models (accuracies increased by 0.04, 0.04 and 0.06 for YFD, YGFW and YWT, respectively). We found promising results for the future transition of the Dohne breed from pedigree to genomic selection. A combined genomic evaluation, with the MERINOSELECT evaluation in addition to using metafounders, is expected to enhance the quality of genomic predictions for the Dohne Merino breed.
多恩美利奴羊于 20 世纪 90 年代从南非引入澳大利亚。它主要用于与美利奴羊杂交,以改善繁殖和胴体成分等特性。从那时起,该品种在澳大利亚不断扩大,但基因分型和表型纯种个体的数量仍然很少,这使基因组选择的准确性受到质疑。另一方面,澳大利亚美利奴在单独的基因组评估(MERINOSELECT)中拥有大量的参考群体。将这些资源结合起来,可以快速追踪基因组选择对小型品种的影响,但其有效性还有待研究。这项研究基于 53663 个基因型和 200 多万个表型的数据集。研究的主要目的是:(1)描述美利奴和多恩美利奴品种的遗传结构特征;(2)从预测质量的角度研究综合评估的效用;(3)比较几种遗传分组方法。我们使用 "LR 法"(线性回归)进行这些评估。我们在研究中发现,不同美利奴品系和多恩品种之间的 Fst 值非常低(低于 0.048),表明遗传分化程度非常低。主成分分析显示出三个不同的群体,即纯种美利奴、纯种多恩和杂交动物。从基于血统的评估到基于基因组的评估,将整个种群作为参照物可获得最佳的预测质量和最大的准确性提高(从 "LR-方法"):一岁犊牛纤维直径(YFD)、一岁犊牛绒毛重量(YGFW)和一岁犊牛活重(YWT)的准确度分别为 0.18、0.14 和 0.16。综合基因组评价的准确度高于仅基于多恩参考的评价(YFD、YGFW 和 YWT 的准确度分别提高了 0.16、0.06 和 0.07)。在综合基因组评估中,元创始人模型比未知亲本组模型更准确(YFD、YGFW 和 YWT 的准确率分别提高了 0.04、0.04 和 0.06)。我们发现,未来多恩品种从血统选育过渡到基因组选育的结果很有希望。除了使用元创始者之外,结合 MERINOSELECT 评估进行基因组评估有望提高多恩美利奴品种的基因组预测质量。
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引用次数: 0
QTL analysis to identify genes involved in the trade-off between silk protein synthesis and larva-pupa transition in silkworms 通过 QTL 分析确定参与家蚕丝蛋白合成和幼虫-蛹过渡之间权衡的基因
IF 4.1 1区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2024-09-30 DOI: 10.1186/s12711-024-00937-z
Rui Gao, Chunlin Li, Ang Zhou, Xiachao Wang, Kupeng Lu, Weidong Zuo, Hai Hu, Minjin Han, Xiaoling Tong, Fangyin Dai
Insect-based food and feed are increasingly attracting attention. As a domesticated insect, the silkworm (Bombyx mori) has a highly nutritious pupa that can be easily raised in large quantities through large-scale farming, making it a highly promising source of food. The ratio of pupa to cocoon (RPC) refers to the proportion of the weight of the cocoon that is attributed to pupae, and is of significant value for edible utilization, as a higher RPC means a higher ratio of conversion of mulberry leaves to pupa. In silkworm production, there is a trade-off between RPC and cocoon shell ratiao(CSR), which refers the ratio of silk protein to the entire cocoon, during metamorphosis process. Understanding the genetic basis of this balance is crucial for breeding edible strains with a high RPC and further advancing its use as feed. Using QTL-seq, we identified a quantitative trait locus (QTL) for the balance between RPC and CSR that is located on chromosome 11 and covers a 9,773,115-bp region. This locus is an artificial selection hot spot that contains ten non-overlapping genomic regions under selection that were involved in the domestication and genetic breeding processes. These regions include 17 genes, nine of which are highly expressed in the silk gland, which is a vital component in the trade-off between RPC and CSR. These genes are annotate with function related with epigenetic modifications and the regulation of DNA replication et al. We identified one and two single nucleotide polymorphisms (SNPs) in the exons of teh KWMTBOMO06541 and KWMTBOMO06485 genes that result in amino acid changes in the protein domains. These SNPs have been strongly selected for during the domestication process. The KWMTBOMO06485 gene encodes the Bombyx mori (Bm) tRNA methyltransferase (BmDnmt2) and its knockout results in a significant change in the trade-off between CSR and RPC in both sexes. Taken together, our results contribute to a better understanding of the genetic basis of RPC and CSR. The identified QTL and genes that affect RPC can be used for marker-assisted and genomic selection of silkworm strains with a high RPC. This will further enhance the production efficiency of silkworms and of closely-related insects for edible and feed purposes.
以昆虫为基础的食品和饲料越来越受到人们的关注。作为一种驯化昆虫,蚕(Bombyx mori)的蛹营养价值很高,可以通过规模化养殖轻松实现大量饲养,是一种极具潜力的食物来源。蚕蛹与蚕茧的比率(RPC)指的是蚕蛹占蚕茧重量的比例,对食用利用具有重要价值,因为 RPC 越高,意味着桑叶转化为蚕蛹的比率越高。在家蚕生产中,RPC 与茧壳率(CSR)之间存在权衡,后者指的是蚕丝蛋白在整个蚕茧中的比例。了解这种平衡的遗传基础对于培育高RPC的可食用品系以及进一步推动其作为饲料的应用至关重要。通过 QTL-seq,我们确定了一个 RPC 和 CSR 之间平衡的数量性状位点(QTL),该位点位于 11 号染色体上,覆盖 9,773,115 bp 的区域。该基因座是一个人工选择热点,包含十个非重叠的基因组选择区域,这些区域参与了驯化和遗传育种过程。这些区域包括 17 个基因,其中 9 个基因在丝腺中高度表达,而丝腺是 RPC 和 CSR 之间权衡的重要组成部分。我们在 KWMTBOMO06541 和 KWMTBOMO06485 基因的外显子中发现了一个和两个单核苷酸多态性(SNPs),它们会导致蛋白质结构域的氨基酸发生变化。在驯化过程中,这些 SNPs 被强烈选择。KWMTBOMO06485 基因编码 Bombyx mori(Bm)的 tRNA 甲基转移酶(BmDnmt2),敲除该基因会导致雌雄雌虫在 CSR 和 RPC 之间的权衡发生显著变化。总之,我们的研究结果有助于更好地理解 RPC 和 CSR 的遗传基础。已鉴定的影响 RPC 的 QTL 和基因可用于标记辅助和基因组选育高 RPC 的蚕品系。这将进一步提高家蚕以及与家蚕密切相关的食用和饲料昆虫的生产效率。
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引用次数: 0
Identification of genomic regions associated with fatty acid metabolism across blood, liver, backfat and muscle in pigs 鉴定猪血液、肝脏、背脂和肌肉中与脂肪酸代谢相关的基因组区域
IF 4.1 1区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2024-09-26 DOI: 10.1186/s12711-024-00933-3
Junhui Liu, Cristina Sebastià, Teodor Jové-Juncà, Raquel Quintanilla, Olga González-Rodríguez, Magí Passols, Anna Castelló, Armand Sánchez, Maria Ballester, Josep M. Folch
The composition and distribution of fatty acids (FA) are important factors determining the quality, flavor, and nutrient value of meat. In addition, FAs synthesized in the body participate in energy metabolism and are involved in different regulatory pathways in the form of signaling molecules or by acting as agonist or antagonist ligands of different nuclear receptors. Finally, synthesis and catabolism of FAs affect adaptive immunity by regulating lymphocyte metabolism. The present study performed genome-wide association studies using FA profiles of blood, liver, backfat and muscle from 432 commercial Duroc pigs. Twenty-five genomic regions located on 15 Sus scrofa chromosomes (SSC) were detected. Annotation of the quantitative trait locus (QTL) regions identified 49 lipid metabolism-related candidate genes. Among these QTLs, four were identified in more than one tissue. The ratio of C20:4n-6/C20:3n-6 was associated with the region on SSC2 at 7.56–14.26 Mb for backfat, liver, and muscle. Members of the fatty acid desaturase gene cluster (FADS1, FADS2, and FADS3) are the most promising candidate genes in this region. Two QTL regions on SSC14 (103.81–115.64 Mb and 100.91–128.14 Mb) were identified for FA desaturation in backfat and muscle. In addition, two separate regions on SSC9 at 0 – 14.55 Mb and on SSC12 at 0–1.91 Mb were both associated with the same multiple FA traits for backfat, with candidate genes involved in de novo FA synthesis and triacylglycerol (TAG) metabolism, such as DGAT2 and FASN. The ratio C20:0/C18:0 was associated with the region on SSC5 at 64.84–78.32 Mb for backfat. Furthermore, the association of the C16:0 content with the region at 118.92–123.95 Mb on SSC4 was blood specific. Finally, candidate genes involved in de novo lipogenesis regulate T cell differentiation and promote the generation of palmitoleate, an adipokine that alleviates inflammation. Several SNPs and candidate genes were associated with lipid metabolism in blood, liver, backfat, and muscle. These results contribute to elucidating the molecular mechanisms implicated in the determination of the FA profile in different pig tissues and can be useful in selection programs that aim to improve health and energy metabolism in pigs.
脂肪酸(FA)的组成和分布是决定肉类品质、风味和营养价值的重要因素。此外,体内合成的脂肪酸参与能量代谢,并以信号分子的形式或作为不同核受体的激动剂或拮抗剂配体参与不同的调节途径。最后,FAs 的合成和分解通过调节淋巴细胞的新陈代谢影响适应性免疫。本研究利用 432 头商品杜洛克猪的血液、肝脏、背膘和肌肉的脂肪酸谱进行了全基因组关联研究。研究检测了位于 15 条苏氏猪染色体(SSC)上的 25 个基因组区域。定量性状位点(QTL)区域的注释确定了 49 个脂质代谢相关的候选基因。在这些 QTLs 中,有 4 个在一个以上的组织中被发现。在背脂、肝脏和肌肉中,C20:4n-6/C20:3n-6的比例与SSC2上7.56-14.26 Mb的区域相关。脂肪酸去饱和酶基因簇成员(FADS1、FADS2 和 FADS3)是该区域最有希望的候选基因。在 SSC14 上的两个 QTL 区域(103.81-115.64 Mb 和 100.91-128.14 Mb)鉴定出了背脂和肌肉中脂肪酸脱饱和的基因。此外,SSC9上0-14.55 Mb和SSC12上0-1.91 Mb的两个独立区域都与背脂中相同的多种FA性状相关,候选基因涉及从头FA合成和三酰甘油(TAG)代谢,如DGAT2和FASN。C20:0/C18:0的比例与背脂的SSC5上64.84-78.32 Mb的区域相关。此外,C16:0 含量与 SSC4 上 118.92-123.95 Mb 区域的关联具有血液特异性。最后,参与新脂肪生成的候选基因能调节 T 细胞分化并促进棕榈油酸盐的生成,棕榈油酸盐是一种能缓解炎症的脂肪因子。一些 SNP 和候选基因与血液、肝脏、背脂和肌肉中的脂质代谢有关。这些结果有助于阐明决定不同猪组织中FA概况的分子机制,并有助于旨在改善猪的健康和能量代谢的选育计划。
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引用次数: 0
A million-cow genome-wide association study of productive life in U.S. Holstein cows 关于美国荷斯坦奶牛生产寿命的百万头奶牛全基因组关联研究
IF 4.1 1区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2024-09-26 DOI: 10.1186/s12711-024-00935-1
Zuoxiang Liang, Dzianis Prakapenka, Hafedh B. Zaabza, Paul M. VanRaden, Curtis P. Van Tassell, Yang Da
Productive life (PL) of a cow is the time the cow remains in the milking herd from first calving to exit from the herd due to culling or death and is an important economic trait in U.S. Holstein cattle. The large samples of Holstein genomic evaluation data that have become available recently provided unprecedented statistical power to identify genetic factors affecting PL in Holstein cows using the approach of genome-wide association study (GWAS). The GWAS analysis used 1,103,641 Holstein cows with phenotypic observations on PL and genotypes of 75,282 single nucleotide polymorphism (SNP) markers. The statistical tests and estimation of SNP additive and dominance effects used the approximate generalized least squares method implemented by the EPISNPmpi computer program. The GWAS detected 5390 significant additive effects of PL distributed over all 29 autosomes and the X–Y nonrecombining region of the X chromosome (Chr31). Two chromosome regions had the most significant and largest cluster of additive effects, the SLC4A4-GC-NPFFR2 (SGN) region of Chr06 with pleiotropic effects for PL, fertility, somatic cell score and milk yield; and the 32–52 Mb region of Chr10 with peak effects for PL in or near RASGRP1 with many important immunity functions. The dominance tests detected 38 significant dominance effects including 12 dominance effects with sharply negative homozygous recessive genotypes on Chr18, Chr05, Chr23 and Chr24. The GWAS results showed that highly significant genetic effects for PL were in chromosome regions known to have highly significant effects for fertility and health and a chromosome region with multiple genes with reproductive and immunity functions. SNPs with rare but sharply negative homozygous recessive genotypes for PL existed and should be used for eliminating heifers carrying those homozygous recessive genotypes.
奶牛的生产寿命(PL)是指奶牛从第一次产犊到因淘汰或死亡而退出挤奶牛群的时间,是美国荷斯坦牛的一个重要经济性状。最近获得的大量荷斯坦基因组评估数据样本为利用全基因组关联研究(GWAS)方法确定影响荷斯坦奶牛PL的遗传因素提供了前所未有的统计能力。GWAS 分析使用了 1,103,641 头荷斯坦奶牛的 PL 表型观测数据和 75,282 个单核苷酸多态性 (SNP) 标记的基因型。对SNP加性效应和显性效应的统计检验和估计采用了EPISNPmpi计算机程序实现的近似广义最小二乘法。GWAS 检测出了 5390 个 PL 的显著加性效应,分布在全部 29 个常染色体和 X 染色体的 X-Y 非重组区(Chr31)。两个染色体区域具有最显著和最大的加性效应群,一个是 Chr06 的 SLC4A4-GC-NPFFR2 (SGN) 区域,该区域对 PL、繁殖力、体细胞评分和产奶量具有多向效应;另一个是 Chr10 的 32-52 Mb 区域,该区域的 PL 在 RASGRP1 或其附近具有峰值效应,而 RASGRP1 具有许多重要的免疫功能。显性检验发现了 38 个显著的显性效应,包括 12 个在 Chr18、Chr05、Chr23 和 Chr24 上具有显著负同源隐性基因型的显性效应。GWAS 结果显示,PL 的高度显著遗传效应位于已知对生育和健康有高度显著影响的染色体区域,以及一个含有多个具有生殖和免疫功能基因的染色体区域。SNPs对PL的同源隐性基因型罕见但呈显著负性,应用于淘汰携带这些同源隐性基因型的小母牛。
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引用次数: 0
Genotyping both live and dead animals to improve post-weaning survival of pigs in breeding programs 对活体和死体动物进行基因分型,提高育种项目中猪断奶后的存活率
IF 4.1 1区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Pub Date : 2024-09-18 DOI: 10.1186/s12711-024-00932-4
Md Sharif-Islam, Julius H. J. van der Werf, Mark Henryon, Thinh Tuan Chu, Benjamin J. Wood, Susanne Hermesch
In this study, we tested whether genotyping both live and dead animals (GSD) realises more genetic gain for post-weaning survival (PWS) in pigs compared to genotyping only live animals (GOS). Stochastic simulation was used to estimate the rate of genetic gain realised by GSD and GOS at a 0.01 rate of pedigree-based inbreeding in three breeding schemes, which differed in PWS (95%, 90% and 50%) and litter size (6 and 10). Pedigree-based selection was conducted as a point of reference. Variance components were estimated and then estimated breeding values (EBV) were obtained in each breeding scheme using a linear or a threshold model. Selection was for a single trait, i.e. PWS with a heritability of 0.02 on the observed scale. The trait was simulated on the underlying scale and was recorded as binary (0/1). Selection candidates were genotyped and phenotyped before selection, with only live candidates eligible for selection. Genotyping strategies differed in the proportion of live and dead animals genotyped, but the phenotypes of all animals were used for predicting EBV of the selection candidates. Based on a 0.01 rate of pedigree-based inbreeding, GSD realised 14 to 33% more genetic gain than GOS for all breeding schemes depending on PWS and litter size. GSD increased the prediction accuracy of EBV for PWS by at least 14% compared to GOS. The use of a linear versus a threshold model did not have an impact on genetic gain for PWS regardless of the genotyping strategy and the bias of the EBV did not differ significantly among genotyping strategies. Genotyping both dead and live animals was more informative than genotyping only live animals to predict the EBV for PWS of selection candidates, but with marginal increases in genetic gain when the proportion of dead animals genotyped was 60% or greater. Therefore, it would be worthwhile to use genomic information on both live and more than 20% dead animals to compute EBV for the genetic improvement of PWS under the assumption that dead animals reflect increased liability on the underlying scale.
在这项研究中,我们测试了与只对活体动物进行基因分型(GOS)相比,同时对活体动物和死体动物进行基因分型(GSD)是否能在猪的断奶后存活率(PWS)方面实现更多的遗传增益。随机模拟估算了在基于血统的近亲繁殖率为 0.01 的情况下,GSD 和 GOS 在三种育种方案中实现的遗传增益率,这三种育种方案在断奶后存活率(95%、90% 和 50%)和窝产仔数(6 和 10)方面存在差异。基于血统的选择是作为参考点进行的。每个育种方案都使用线性或阈值模型对变异成分进行估计,然后获得估计育种值(EBV)。选择针对的是单一性状,即在观察尺度上遗传率为 0.02 的 PWS。该性状在基础量表上进行模拟,并记录为二元性状(0/1)。候选品种在选育前要进行基因分型和表型分析,只有活体候选品种才有资格参加选育。基因分型策略在活体和死体动物的基因分型比例上有所不同,但所有动物的表型都用于预测候选样本的 EBV。基于 0.01 的近亲繁殖率,在所有育种方案中,GSD 实现的遗传增益比 GOS 高 14% 至 33%,具体取决于 PWS 和产仔数。与 GOS 相比,GSD 对 PWS 的 EBV 预测准确率至少提高了 14%。无论采用哪种基因分型策略,线性模型和阈值模型的使用对PWS的遗传增益都没有影响,而且不同基因分型策略的EBV偏差也没有显著差异。与只对活体动物进行基因分型相比,同时对死体动物和活体动物进行基因分型更能预测候选动物PWS的EBV,但当死体动物的基因分型比例达到或超过60%时,遗传增益的增加微乎其微。因此,值得使用活体动物和超过 20% 死体动物的基因组信息来计算 PWS 遗传改良的 EBV,前提是死体动物反映了基本规模上责任的增加。
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Genetics Selection Evolution
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