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Measuring individual inbreeding in the age of genomics: marker-based measures are better than pedigrees.

ABSTRACT: Inbreeding (mating between relatives) can dramatically reduce the fitness of offspring by causing parts of the genome to be identical by descent. Thus, measuring individual inbreeding is crucial for ecology, evolution and conservation biology. We used computer simulations to test whether the realized proportion of the genome that is identical by descent (IBDG) is predicted better by the pedigree inbreeding coefficient (FP) or by genomic (marker-based) measures of inbreeding. Genomic estimators of IBDG included the increase in individual homozygosity relative to mean Hardy-Weinberg expected homozygosity (FH), and two measures (FROH and FE) that use mapped genetic markers to estimate IBDG. IBDG was more strongly correlated with FH, FE and FROH than with FP across a broad range of simulated scenarios when thousands of SNPs were used. For example, IBDG was more strongly correlated with FROH, FH and FE (estimated with ?10?000 SNPs) than with FP (estimated with 20 generations of complete pedigree) in populations with a recent reduction in the effective populations size (from Ne=500 to Ne=75). FROH, FH and FE generally explained >90% of the variance in IBDG (among individuals) when 35?K or more SNPs were used. FP explained <80% of the variation in IBDG on average in all simulated scenarios, even when pedigrees included 20 generations. Our results demonstrate that IBDG can be more precisely estimated with large numbers of genetic markers than with pedigrees. We encourage researchers to adopt genomic marker-based measures of IBDG as thousands of loci can now be genotyped in any species.

SUBMITTER: Kardos M

PROVIDER: S-EPMC4815495 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Measuring individual inbreeding in the age of genomics: marker-based measures are better than pedigrees.

Kardos M M Luikart G G Allendorf F W FW

Heredity 20150318 1

Inbreeding (mating between relatives) can dramatically reduce the fitness of offspring by causing parts of the genome to be identical by descent. Thus, measuring individual inbreeding is crucial for ecology, evolution and conservation biology. We used computer simulations to test whether the realized proportion of the genome that is identical by descent (IBDG) is predicted better by the pedigree inbreeding coefficient (FP) or by genomic (marker-based) measures of inbreeding. Genomic estimators o ...[more]

PMID: 26059970

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Project description:Inbreeding coefficients can be estimated either from pedigree data or from genomic data, and with genomic data, they are either global or local (when the linkage map is used). Recently, we developed a new hidden Markov model (HMM) that estimates probabilities of homozygosity-by-descent (HBD) at each marker position and automatically partitions autozygosity in multiple age-related classes (based on the length of HBD segments). Our objectives were to: (1) characterize inbreeding with our model in an intensively selected population such as the Belgian Blue Beef (BBB) cattle breed; (2) compare the properties of the model at different marker densities; and (3) compare our model with other methods.When using 600 K single nucleotide polymorphisms (SNPs), the inbreeding coefficient (probability of sampling an HBD locus in an individual) was on average 0.303 (ranging from 0.258 to 0.375). HBD-classes associated to historical ancestors (with small segments ? 200 kb) accounted for 21.6% of the genome length (71.4% of the total length of the genome in HBD segments), whereas classes associated to more recent ancestors accounted for only 22.6% of the total length of the genome in HBD segments. However, these recent classes presented more individual variation than more ancient classes. Although inbreeding coefficients obtained with low SNP densities (7 and 32 K) were much lower (0.060 and 0.093), they were highly correlated with those obtained at higher density (r = 0.934 and 0.975, respectively), indicating that they captured most of the individual variation. At higher SNP density, smaller HBD segments are identified and, thus, more past generations can be explored. We observed very high correlations between our estimates and those based on homozygosity (r = 0.95) or on runs-of-homozygosity (r = 0.95). As expected, pedigree-based estimates were mainly correlated with recent HBD-classes (r = 0.56).Although we observed high levels of autozygosity associated with small HBD segments in BBB cattle, recent inbreeding accounted for most of the individual variation. Recent autozygosity can be captured efficiently with low-density SNP arrays and relatively simple models (e.g., two HBD classes). The HMM framework provides local HBD probabilities that are still useful at lower SNP densities.

Project description:BackgroundThe 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).ResultsIf 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.ConclusionsWhen 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.

Dataset Information

Measuring individual inbreeding in the age of genomics: marker-based measures are better than pedigrees.

Publications

Measuring individual inbreeding in the age of genomics: marker-based measures are better than pedigrees.

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