An evaluation of inbreeding measures using a whole genome sequenced cattle pedigree

The estimation of the inbreeding coefficient (F) is essential for the
study of inbreeding depression (ID) or for the management of populations
under conservation. Several methods have been proposed to estimate the
realized F using genetic markers, but it remains unclear which one should
be used. Here we used whole-genome sequence data for 245 individuals from
a Holstein cattle pedigree to empirically evaluate which estimators best
capture homozygosity at variants causing ID, such as rare deleterious
alleles or loci presenting heterozygote advantage and segregating at
intermediate frequency. Estimators relying on the correlation between
uniting gametes (FUNI) or on the genomic relationships (FGRM) presented
the highest correlations with these variants. However, homozygosity at
rare alleles remained poorly captured. A second group of estimators
relying on excess homozygosity (FHOM), homozygous-by-descent segments
(FHBD), runs-of-homozygosity (FROH) or on the known genealogy (FPED) was
better at capturing whole genome homozygosity, reflecting the consequences
of inbreeding on all variants, and for young alleles with low to moderate
frequencies. The results indicate that FUNI and FGRM might present a
stronger association with ID. However, the situation might be different
when recessive deleterious alleles reach higher frequencies, such as in
populations with a small effective population size. For locus specific
inbreeding measures or at low marker density, the ranking of the methods
can also change as FHBD makes better use of the information from
neighbouring markers. Finally, we confirmed that genomic measures are in
general superior to pedigree-based estimates. In particular, FPED was
uncorrelated with locus specific homozygosity.