A heuristic method to identify runs of homozygosity associated with reduced performance in livestock

Although, for the most part, genome-wide metrics are currently used in managing livestock inbreeding, genomic data offer, in principle, the ability to identify functional inbreeding. Here, we present a heuristic method to identify haplotypes contained within a run of homozygosity (ROH) associated with reduced performance. Results are presented for simulated and swine data. The algorithm comprises 3 steps. Step 1 scans the genome based on marker windows of decreasing size and identifies ROH genotypes associated with an unfavorable phenotype. Within this stage, multiple aggregation steps reduce the haplotype to the smallest possible length. In step 2, the resulting regions are formally tested for significance with the use of a linear mixed model. Lastly, step 3 removes nested windows. The effect of the unfavorable haplotypes identified and their associated haplotype probabilities for a progeny of a given mating pair or an individual can be used to generate an inbreeding load matrix (ILM). Diagonals of ILM characterize the functional individual inbreeding load (IIL). We estimated the accuracy of predicting the phenotype based on IIL. We further compared the significance of the regression coefficient for IIL on phenotypes with genome-wide inbreeding metrics. We tested the algorithm using simulated scenarios (12 scenarios), combining different levels of linkage disequilibrium (LD) and number of loci impacting a quantitative trait. Additionally, we investigated 9 traits from 2 maternal purebred swine lines. In simulated data, as the LD in the population increased, the algorithm identified a greater proportion of the true unfavorable ROH effects. For example, the proportion of highly unfavorable true ROH effects identified rose from 32 to 41% for the low-to the high-LD scenario. In both simulated and real data, the haplotypes identified were contained within a much larger ROH (9.12-12.1 Mb). The IIL prediction accuracy was greater than 0 across all scenarios for simulated data (mean of 0.49 [95% confidence interval 0.47-0.52] for the high-LD scenario) and for nearly all swine traits (mean of 0.17 [SD 0.10]). On average, across simulated and swine data sets, the IIL regression coefficient was more closely related to progeny performance than any genome-wide inbreeding metric. A heuristic method was developed that identified ROH genotypes with reduced performance and characterized the combined effects of ROH genotypes within and across individuals.