Targeted allele frequency tuning in breeding populations via alternative optimum contribution selection

When managing the rate of genomic inbreeding using genomic relationship matrices, allele frequencies tend to be moved toward the frequencies used for centering genotypes in those matrices. Here, we explore if this behavior could be exploited to purposefully change the frequency of alleles. We test the method in a simulated toy example and in the Friesian horse population to purge deleterious alleles as a case study. We show that the average entry of the numerator matrix from VanRaden's method 1 (ZZ'¯) equals 4 times the average squared difference between the populations' allele frequency (AF) and the used centering allele frequency (CAF) (ZZ'¯=4∑k=1nsnp(AFk-CAFk)2). By setting the centering frequency to the desired AF and subsequently optimizing contributions to minimize the average matrix entry, the population's AF is shifted to the desired frequency. We call this novel selection method using a matrix: "TAFT" (targeted allele frequency tuning), and use it with optimum contribution selection (OCS) in this study (TAFT-OCS). TAFT outperformed index methods for target frequencies between 0% and 100%. The index methods showed different behavior compared to TAFT by exerting different selection pressure on loci depending on the difference to the target frequency. Frequencies of all 12 deleterious alleles could be reduced within ∼6 generations in the Friesian horse population so that no affected individuals remained. At the same time, genetic gain of 3.7 cm withers height (1.11 gSD) per generation was made and the realized pedigree inbreeding rate kept below 0.5%. We propose TAFT-OCS as a novel method to directly change allele frequencies to any desired value which is particularly beneficial if intermediate allele frequencies are desired or genetic diversity should be maintained. TAFT shifts the focus of selection from individuals to alleles. It only requires to set a desired target frequency and a minimum and maximum allowed frequency if needed.