Department of Animal and Dairy Science, University of Georgia, Athens, GA.
Beltsville Agricultural Research Center, USDA Agricultural Research Service, Beltsville, MD.
J Anim Sci. 2020 Dec 1;98(12). doi: 10.1093/jas/skaa361.
Pedigree information was traditionally used to assess inbreeding. The availability of high-density marker panels provides an alternative to assess inbreeding, particularly in the presence of incomplete and error-prone pedigrees. Assessment of autozygosity across chromosomal segments using runs of homozygosity (ROH) has emerged as a valuable tool to estimate inbreeding due to its general flexibility and ability to quantify the chromosomal contribution to genome-wide inbreeding. Unfortunately, the identification of ROH segments is sensitive to the parameters used during the search process. These parameters are heuristically set, leading to significant variation in the results. The minimum length required to identify an ROH segment has major effects on the estimation of inbreeding and inbreeding depression, yet it is arbitrarily set. To overcome this limitation, a search algorithm to approximate mutation enrichment was developed to determine the minimum length of ROH segments. It consists of finding genome segments with significant effect differences in trait means between animals with high and low burdens of autozygous intervals with a specific length. The minimum length could be determined heuristically as the smallest interval at which a significant signal is detected. The proposed method was tested in an inbred Hereford cattle population genotyped for 30,220 SNPs. Phenotypes recorded for six traits were used for the approximation of mutation loads. The estimated minimum length was around 1 Mb for yearling weight (YW) and average daily gain (ADG) and 4 Mb for birth weight and weaning weight. These trait-specific thresholds estimated using the proposed method could be attributed to a trait-dependent effect of homozygosity. The detection of significant inbreeding effects was well aligned with the estimated thresholds, especially for YW and ADG. Although highly deleterious alleles are expected to be more frequent in recent inbreeding (long ROH), short ROH segments (<5 Mb) could contain a large number of less deleterious mutations with substantial joint effects on some traits (YW and ADG). Our results highlight the importance of accurate estimation of the ROH-based inbreeding and the necessity to consider a trait-specific minimum length threshold for the identification of ROH segments in inbreeding depression analyses. These thresholds could be determined using the proposed method provided the availability of phenotypic information.
系谱信息传统上用于评估近交。高密度标记面板的可用性提供了评估近交的替代方法，特别是在存在不完整和易错的系谱的情况下。使用纯合段（ROH）评估染色体片段中的自交可以作为一种估计近交的有价值的工具，因为它具有通用性和量化基因组范围内近交的染色体贡献的能力。不幸的是，ROH 片段的识别对搜索过程中使用的参数敏感。这些参数是启发式设置的，导致结果存在显著差异。确定 ROH 片段所需的最小长度对近交和近交衰退的估计有重大影响，但它是任意设置的。为了克服这一限制，开发了一种搜索算法来近似突变富集，以确定 ROH 片段的最小长度。它包括在具有特定长度的高自交负担和低自交负担的动物之间，在性状均值上找到具有显著效应差异的基因组片段。最小长度可以通过启发式方法确定为检测到显著信号的最小间隔。该方法在 30,220 个 SNP 基因型的近交荷斯坦牛群体中进行了测试。用于近似突变负荷的六个性状的表型记录。对于周岁体重（YW）和平均日增重（ADG），估计的最小长度约为 1 Mb，对于初生重和断奶重，估计的最小长度约为 4 Mb。使用所提出的方法估计的这些特定于性状的阈值可以归因于与纯合性相关的性状依赖效应。显著近交效应的检测与估计的阈值非常吻合，尤其是对于 YW 和 ADG。尽管高度有害的等位基因预计在最近的近交中更为常见（长 ROH），但短的 ROH 片段（<5 Mb）可能包含大量较少有害的突变，对某些性状（YW 和 ADG）有较大的联合效应。我们的结果强调了准确估计基于 ROH 的近交的重要性，以及在近交衰退分析中识别 ROH 片段时考虑特定于性状的最小长度阈值的必要性。可以使用提供表型信息的所提出的方法来确定这些阈值。
