The estimation of the inbreeding coefficient (F) is essential for the study of inbreeding depression (ID) or for the management of populations under conservation. Several methods have been proposed to estimate the realized F using genetic markers, but it remains unclear which one should be used. Here we used whole-genome sequence data for 245 individuals from a Holstein cattle pedigree to empirically evaluate which estimators best capture homozygosity at variants causing ID, such as rare deleterious alleles or loci presenting heterozygote advantage and segregating at intermediate frequency. Estimators relying on the correlation between uniting gametes (FUNI) or on the genomic relationships (FGRM) presented the highest correlations with these variants. However, homozygosity at rare alleles remained poorly captured. A second group of estimators relying on excess homozygosity (FHOM), homozygous-by-descent segments (FHBD), runs-of-homozygosity (FROH) or on the known genealogy (FPED) was better at capturing whole-genome homozygosity, reflecting the consequences of inbreeding on all variants, and for young alleles with low to moderate frequencies (0.10 < . < 0.25). The results indicate that FUNI and FGRM might present a stronger association with ID. However, the situation might be different when recessive deleterious alleles reach higher frequencies, such as in populations with a small effective population size. For locus-specific inbreeding measures or at low marker density, the ranking of the methods can also change as FHBD makes better use of the information from neighboring markers. Finally, we confirmed that genomic measures are in general superior to pedigree-based estimates. In particular, FPED was uncorrelated with locus-specific homozygosity.

中文翻译：

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使用全基因组测序的牛谱系评估近亲繁殖措施

近交系数 (F) 的估计对于近交衰退 (ID) 的研究或受保护种群的管理至关重要。已经提出了几种使用遗传标记来估计实现的 F 的方法，但仍不清楚应该使用哪一种。在这里，我们使用来自荷斯坦牛谱系的 245 个个体的全基因组序列数据来凭经验评估哪些估计量最能捕捉导致 ID 的变体的纯合性，例如罕见的有害等位基因或呈现杂合子优势并以中频分离的基因座。依赖联合配子 (FUNI) 或基因组关系 (FGRM) 之间相关性的估计器与这些变体的相关性最高。然而，稀有等位基因的纯合性仍然很差。第二组依赖于过度纯合性 (FHOM)、纯合子下降片段 (FHBD)、纯合性运行 (FROH) 或已知家谱 (FPED) 的估计量在捕获全基因组纯合性方面表现更好，反映了近亲繁殖对所有变体以及低到中等频率 (0.10 < . < 0.25) 的年轻等位基因的影响。结果表明，FUNI 和 FGRM 可能与 ID 表现出更强的关联。然而，当隐性有害等位基因达到较高频率时，例如在有效种群规模较小的种群中，情况可能会有所不同。对于特定位点的近交测量或低标记密度，随着 FHBD 更好地利用来自相邻标记的信息，方法的排名也会发生变化。最后，我们证实，基因组测量通常优于基于谱系的估计。特别是，FPED 与位点特异性纯合性不相关。