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Metafounders are Fst fixation indices and reduce bias in single step genomic evaluations

Carolina Andrea Garcia-Baccino, View ORCID ProfileAndres Legarra, Ole F Christensen, View ORCID ProfileIgnacy Misztal, View ORCID ProfileIvan Pocrnic, Zulma G Vitezica, View ORCID ProfileRodolfo J.C. Cantet
doi: https://doi.org/10.1101/083675
Carolina Andrea Garcia-Baccino
*Departamento de Producción Animal, Facultad de Agronomía, Universidad de Buenos Aires, C1417DSE Buenos Aires, Argentina
§§Instituto de Investigaciones en Producción Animal - Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
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Andres Legarra
§INRA, GenPhySE (Génétique, Physiologie et Systèmes d’Elevage), F-31326 Castanet-Tolosan, France
†Université de Toulouse, INP, ENSAT, GenPhySE (Génétique, Physiologie et Systèmes d’Elevage), F-31326 Castanet-Tolosan, France
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Ole F Christensen
**Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University, DK-8830 Tjele, Denmark
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Ignacy Misztal
‡Animal and Dairy Science, University of Georgia, 30602 Athens, GA, USA
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Ivan Pocrnic
‡Animal and Dairy Science, University of Georgia, 30602 Athens, GA, USA
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Zulma G Vitezica
§INRA, GenPhySE (Génétique, Physiologie et Systèmes d’Elevage), F-31326 Castanet-Tolosan, France
†Université de Toulouse, INP, ENSAT, GenPhySE (Génétique, Physiologie et Systèmes d’Elevage), F-31326 Castanet-Tolosan, France
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Rodolfo J.C. Cantet
*Departamento de Producción Animal, Facultad de Agronomía, Universidad de Buenos Aires, C1417DSE Buenos Aires, Argentina
§§Instituto de Investigaciones en Producción Animal - Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
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ABSTRACT

BACKGROUND Metafounders are pseudo-individuals that condense the genetic heterozygosity and relationships within and across base pedigree populations, i.e. ancestral populations. This work addresses estimation and usefulness of metafounder relationships in Single Step GBLUP.

RESULTS We show that the ancestral relationship parameters are proportional to standardized covariances of base allelic frequencies across populations, like Fst fixation indexes. These covariances of base allelic frequencies can be estimated from marker genotypes of related recent individuals, and pedigree. Simple methods for estimation include naïve computation of allele frequencies from marker genotypes or a method of moments equating average pedigree-based and marker-based relationships. Complex methods include generalized least squares or maximum likelihood based on pedigree relationships. To our knowledge, methods to infer Fst coefficients and Fst differentiation have not been developed for related populations.

A compatible genomic relationship matrix constructed as a crossproduct of {−1,0,1} codes, and equivalent (up to scale factors) to an identity by state relationship matrix at the markers, is derived. Using a simulation with a single population under selection, in which only males and youngest animals were genotyped, we observed that generalized least squares or maximum likelihood gave accurate and unbiased estimates of the ancestral relationship parameter (true value: 0.40) whereas the other two (naïve and method of moments) were biased (estimates of 0.43 and 0.35). We also observed that genomic evaluation by Single Step GBLUP using metafounders was less biased in terms of accurate genetic trend (0.01 instead of 0.12 bias), slightly overdispersed (0.94 instead of 0.99) and as accurate (0.74) than the regular Single Step GBLUP. Single Step GBLUP using metafounders also provided consistent estimates of heritability.

CONCLUSIONS Estimation of metafounder relationship can be achieved using BLUP-like methods with pedigree and markers. Inclusion of metafounder relationships improves bias of genomic predictions with no loss in accuracy.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted October 26, 2016.
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Metafounders are Fst fixation indices and reduce bias in single step genomic evaluations
Carolina Andrea Garcia-Baccino, Andres Legarra, Ole F Christensen, Ignacy Misztal, Ivan Pocrnic, Zulma G Vitezica, Rodolfo J.C. Cantet
bioRxiv 083675; doi: https://doi.org/10.1101/083675
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Metafounders are Fst fixation indices and reduce bias in single step genomic evaluations
Carolina Andrea Garcia-Baccino, Andres Legarra, Ole F Christensen, Ignacy Misztal, Ivan Pocrnic, Zulma G Vitezica, Rodolfo J.C. Cantet
bioRxiv 083675; doi: https://doi.org/10.1101/083675

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