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关于具有大规模深度系谱的小鼠生长遗传参数的可识别性

On the Identifiability of Genetic Parameters for Growth in Mice With a Massively Deep Pedigree.

作者信息

Ding X, Musa A A, Reinsch N

机构信息

Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.

出版信息

J Anim Breed Genet. 2025 Nov;142(6):706-717. doi: 10.1111/jbg.12938. Epub 2025 May 2.

Abstract

In models with direct and maternal genetic effects, structural features of the data are a potential source of bias and low accuracy of estimates for genetic covariance parameters. One of the well-known reasons for such poor practical identifiability is the lack of dams with own observations. So far, however, no attention has been paid to the impact close relationships may have. Therefore, this genetic-statistical analysis of growth traits in two unselected mouse lines includes investigations on practical identifiability of genetic (co-)variances in the light of the observed high levels of co-ancestry, resulting from massively deep pedigrees. Body weight data had been collected over 33 years (from 1978 to 2011; 145 and 118 generations per line), amounting to approximately 115,000 observations in total for body weight at three developmental stages. Additional analyses of simulated data using the original pedigree structure of one line provided insight into the bias and precision of estimates. Further, closeness to pair-wise structural non-identifiability of genetic (co-)variances was quantified. In univariate analyses, we found genetic correlations between direct and maternal effects all positive for body mass traits at different ages up to mating, except for a single small negative estimate. Overall, multivariate analyses returned somewhat stronger correlations, whereby signs remained unchanged. Simulations showed a tendency toward an upward bias of the direct-maternal genetic correlations and other parameters, especially when the true correlations were higher. For all traits indicators for structural non-identifiability were narrowly close (> 0.998) to unity, the point at which a pair of covariance components no longer can be identified. This narrowness was stronger for separate partitions of data from later generations with higher average inbreeding and within-generation co-ancestry. In conclusion, in models with direct and maternal genetic effects, strong co-ancestry between parents is another feature of the data structure that may result in bias and inflated standard errors of estimated genetic parameters.

摘要

在具有直接遗传效应和母体遗传效应的模型中,数据的结构特征是遗传协方差参数估计产生偏差和低准确性的潜在来源。这种实际可识别性差的一个众所周知的原因是缺乏有自身观测值的母鼠。然而,到目前为止,尚未关注近亲关系可能产生的影响。因此,对两个未经过选择的小鼠品系生长性状进行的这种遗传统计分析,包括根据大量深度系谱所导致的高共同祖先水平,对遗传(协)方差的实际可识别性进行研究。体重数据收集了33年(从1978年到2011年;每个品系145代和118代),三个发育阶段的体重观测值总计约115,000个。使用一个品系的原始系谱结构对模拟数据进行的额外分析,深入了解了估计的偏差和精度。此外,对遗传(协)方差成对结构不可识别性的接近程度进行了量化。在单变量分析中,我们发现直到交配时不同年龄的体重性状的直接效应和母体效应之间的遗传相关性均为正,只有一个小的负估计值除外。总体而言,多变量分析得出的相关性略强,符号保持不变。模拟显示直接-母体遗传相关性和其他参数有向上偏差的趋势,尤其是当真实相关性较高时。对于所有性状,结构不可识别性的指标都非常接近(>0.998)于1,即一对协方差分量不再能够被识别的点。对于来自平均近亲繁殖率较高和代内共同祖先水平较高的后代的数据单独划分,这种接近程度更强。总之,在具有直接遗传效应和母体遗传效应的模型中,亲本之间强烈的共同祖先关系是数据结构的另一个特征,可能导致估计的遗传参数出现偏差和标准误差膨胀。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d250/12501679/1521cb13652b/JBG-142-706-g001.jpg

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