A comparison of marker-based estimators of inbreeding and inbreeding depression

Abstract

Background The availability of genome-wide marker data allows estimation of inbreeding coefficients (F, the probability of identity-by-descent, IBD) and, in turn, estimation of the rate of inbreeding depression (ΔID). We investigated, by computer simulations, the accuracy of the most popular estimators of inbreeding based on molecular markers when computing F and ΔID in populations under random mating, equalization of parental contributions, and artificially selected populations. We assessed estimators described by Li and Horvitz (FLH1 and FLH2), VanRaden (FVR1 and FVR2), Yang and colleagues (FYA1 and FYA2), marker homozygosity (FHOM), runs of homozygosity (FROH) and estimates based on pedigree (FPED) in comparison with estimates obtained from IBD measures (FIBD). Results If the allele frequencies of a base population taken as a reference for the computation of inbreeding are known, all estimators based on marker allele frequencies are highly correlated with FIBD and provide accurate estimates of the mean ΔID. If base population allele frequencies are unknown and current frequencies are used in the estimations, the largest correlation with FIBD is generally obtained by FLH1 and the best estimator of ΔID is FYA2. The estimators FVR2 and FLH2 have the poorest performance in most scenarios. The assumption that base population allele frequencies are equal to 0.5 results in very biased estimates of the average inbreeding coefficient but they are highly correlated with FIBD and give relatively good estimates of ΔID. Estimates obtained directly from marker homozygosity (FHOM) substantially overestimated ΔID. Estimates based on runs of homozygosity (FROH) provide accurate estimates of inbreeding and ΔID. Finally, estimates based on pedigree (FPED) show a lower correlation with FIBD than molecular estimators but provide rather accurate estimates of ΔID. An analysis of data from a pig population supports the main findings of the simulations. Conclusions When base population allele frequencies are known, all marker-allele frequency-based estimators of inbreeding coefficients generally show a high correlation with FIBD and provide good estimates of ΔID. When base population allele frequencies are unknown, FLH1 is the marker frequency-based estimator that is most correlated with FIBD, and FYA2 provides the most accurate estimates of ΔID. Estimates from FROH are also very precise in most scenarios. The estimators FVR2 and FLH2 have the poorest performances.

Detecting inbreeding depression in structured populations

“…As expected, when we subsampled individuals from the PEDIGREE population, RMSE values associated with estimation increased slightly for both LMM AS and LMM GCTA W mixed models and we failed to detect ID in some replicates. Accordingly, despite improving the estimation of relative to the LM, the LMM AS model lacks power with smaller sample sizes (50, 100, 250, 500, and 2,500 individuals): it failed to detect ID by estimating in 26% of replicates and several thousands of individuals would be required to detect ID efficiently (i.e., in all replicates) as Keller et al ( 26 ) and Caballero et al ( 45 ) previously pointed out. With the LMM GCTA U mixed model, all inbreeding coefficients but and had convergence issues, suggesting that the LMM GCTA U mixed model is the least robust of the three mixed models.…”

Genome-wide detections for runs of homozygosity and selective signatures reveal novel candidate genes under domestication in chickens

“…Additionally, a high correlation between F ROH and other indices (F GRM , F HOM , and F UNI ) was found, which was highly consistent with previous reports in modern chickens and other farm animals [ 53 – 56 ]. This also proved that F ROH is more accurate in assessing inbreeding status based on identity by descent [ 57 ].…”

Management of Genetic Diversity in Conservation Programs Using Genomic Coancestry

“…When allele frequencies in the base population (assumed to be constituted by non-inbred and unrelated individuals) are known, frequency-based coefficients are expected to provide unbiased estimates of the average IBD measures of relatedness relative to the base population Caballero et al, 2022). In Chapter 1, only genotype data from two generations (parents and offspring) were available and thus the base population considered was the parental generation.…”

“…used a similar measure and also one based on the realized genomic relationship matrix proposed by . However, many other measures of genomic coancestry (and inbreeding) have been proposed Caballero et al, 2022) and their efficiency when used in OC for maintaining diversity and controlling inbreeding need to be evaluated.…”

“…A third category corresponds to coancestry measures obtained from different realized genomic relationship matrices that have been widely used in genome-wide evaluations and genome-wide association studies. These matrices have been also widely used to obtain genomic inbreeding coefficients (e.g., Keller et al, 2011;Bjelland et al, 2013;Pryce et al, 2014;Zhang et al, 2015;Mastrangelo et al, 2016;Solé et al, 2017;Caballero et al, 2020;Caballero et al, 2022).…”