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Meiotic recombination shapes precision of pedigree- and marker-based estimates of inbreeding.

ABSTRACT: The proportion of an individual's genome that is identical by descent (GWIBD) can be estimated from pedigrees (inbreeding coefficient 'Pedigree F') or molecular markers ('Marker F'), but both estimators come with error. Assuming unrelated pedigree founders, Pedigree F is the expected proportion of GWIBD given a specific inbreeding constellation. Meiotic recombination introduces variation around that expectation (Mendelian noise) and related pedigree founders systematically bias Pedigree F downward. Marker F is an estimate of the actual proportion of GWIBD but it suffers from the sampling error of markers plus the error that occurs when a marker is homozygous without reflecting common ancestry (identical by state). We here show via simulation of a zebra finch and a human linkage map that three aspects of meiotic recombination (independent assortment of chromosomes, number of crossovers and their distribution along chromosomes) contribute to variation in GWIBD and thus the precision of Pedigree and Marker F. In zebra finches, where the genome contains large blocks that are rarely broken up by recombination, the Mendelian noise was large (nearly twofold larger s.d. values compared with humans) and Pedigree F thus less precise than in humans, where crossovers are distributed more uniformly along chromosomes. Effects of meiotic recombination on Marker F were reversed, such that the same number of molecular markers yielded more precise estimates of GWIBD in zebra finches than in humans. As a consequence, in species inheriting large blocks that rarely recombine, even small numbers of microsatellite markers will often be more informative about inbreeding and fitness than large pedigrees.

SUBMITTER: Knief U

PROVIDER: S-EPMC5315531 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Meiotic recombination shapes precision of pedigree- and marker-based estimates of inbreeding.

Knief U U Kempenaers B B Forstmeier W W

Heredity 20161102 3

The proportion of an individual's genome that is identical by descent (GWIBD) can be estimated from pedigrees (inbreeding coefficient 'Pedigree F') or molecular markers ('Marker F'), but both estimators come with error. Assuming unrelated pedigree founders, Pedigree F is the expected proportion of GWIBD given a specific inbreeding constellation. Meiotic recombination introduces variation around that expectation (Mendelian noise) and related pedigree founders systematically bias Pedigree F downwa ...[more]

PMID: 27804967

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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

Meiotic recombination shapes precision of pedigree- and marker-based estimates of inbreeding.

Publications

Meiotic recombination shapes precision of pedigree- and marker-based estimates of inbreeding.

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