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Nonequivalent lethal equivalents: Models and inbreeding metrics for unbiased estimation of inbreeding load.

ABSTRACT: Inbreeding depression, the deterioration in mean trait value in progeny of related parents, is a fundamental quantity in genetics, evolutionary biology, animal and plant breeding, and conservation biology. The magnitude of inbreeding depression can be quantified by the inbreeding load, typically measured in numbers of lethal equivalents, a population genetic quantity that allows for comparisons between environments, populations or species. However, there is as yet no quantitative assessment of which combinations of statistical models and metrics of inbreeding can yield such estimates. Here, we review statistical models that have been used to estimate inbreeding load and use population genetic simulations to investigate how unbiased estimates can be obtained using genomic and pedigree-based metrics of inbreeding. We use simulated binary viability data (i.e., dead versus alive) as our example, but the concepts apply to any trait that exhibits inbreeding depression. We show that the increasingly popular generalized linear models with logit link do not provide comparable and unbiased population genetic measures of inbreeding load, independent of the metric of inbreeding used. Runs of homozygosity result in unbiased estimates of inbreeding load, whereas inbreeding measured from pedigrees results in slight overestimates. Due to widespread use of models that do not yield unbiased measures of the inbreeding load, some estimates in the literature cannot be compared meaningfully. We surveyed the literature for reliable estimates of the mean inbreeding load from wild vertebrate populations and found an average of 3.5 haploid lethal equivalents for survival to sexual maturity. To obtain comparable estimates, we encourage researchers to use generalized linear models with logarithmic links or maximum-likelihood estimation of the exponential equation, and inbreeding coefficients calculated from runs of homozygosity, provided an assembled reference genome of sufficient quality and enough genetic marker data are available.

SUBMITTER: Nietlisbach P

PROVIDER: S-EPMC6346663 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Nonequivalent lethal equivalents: Models and inbreeding metrics for unbiased estimation of inbreeding load.

Nietlisbach Pirmin P Muff Stefanie S Reid Jane M JM Whitlock Michael C MC Keller Lukas F LF

Evolutionary applications 20181023 2

Inbreeding depression, the deterioration in mean trait value in progeny of related parents, is a fundamental quantity in genetics, evolutionary biology, animal and plant breeding, and conservation biology. The magnitude of inbreeding depression can be quantified by the inbreeding load, typically measured in numbers of lethal equivalents, a population genetic quantity that allows for comparisons between environments, populations or species. However, there is as yet no quantitative assessment of w ...[more]

PMID: 30697338

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Project description:BackgroundGenomic technologies, such as high-throughput genotyping based on SNP arrays, have great potential to decipher the genetic architecture of complex traits and provide background information concerning genome structure in domestic animals, including the extent of linkage disequilibrium (LD) and haplotype blocks. The objective of this study was to estimate LD, the population evolution (past effective population size) and the level of inbreeding in Spanish Churra sheep.ResultsA total of 43,784 SNPs distributed in the ovine autosomal genome was analyzed in 1,681 Churra ewes. LD was assessed by measuring r2 between all pairs of loci. For SNPs up to 10 ?kb apart, the average r2 was 0.329; for SNPs separated by 200-500? kb the average r2 was 0.061. When SNPs are separated by more than 50 Mbp, the average r2 is the same as between non-syntenic SNP pairs (0.003). The effective population size has decreased through time, faster from 1,000 to 100 ?years ago and slower since the selection scheme started (15-25 generations ago). In the last generation, four years ago, the effective population size was estimated to be 128 animals. Inbreeding coefficients, although differed depending on the estimation approaches, were generally low and showed the same trend, which indicates that since 2003, inbreeding has been slightly increasing in the studied resource population.ConclusionsThe extent of LD in Churra sheep persists over much more limited distances than reported in dairy cattle and seems to be similar to other ovine populations. Churra sheep show a wide genetic base, with a long-term viable effective population size that has been slightly decreasing since selection scheme began in 1986. The genomic dataset analyzed provided useful information for identifying low-level inbreeding in the sample, whereas based on the parameters reported here, a higher marker density than that analyzed here will be needed to successfully conduct accurate mapping of genes underlying production traits and genomic selection prediction in this sheep breed. Although the Ovine Assembly development is still in a draft stage and future refinements will provide a more accurate physical map that will improve LD estimations, this work is a first step towards the understanding of the genetic architecture in sheep.

Dataset Information

Nonequivalent lethal equivalents: Models and inbreeding metrics for unbiased estimation of inbreeding load.

Publications

Nonequivalent lethal equivalents: Models and inbreeding metrics for unbiased estimation of inbreeding load.

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