Management of Genetic Diversity in the Era of Genomics

Abstract

Management of genetic diversity aims to (i) maintain heterozygosity, which ameliorates inbreeding depression and loss of genetic variation at loci that may become of importance in the future; and (ii) avoid genetic drift, which prevents deleterious recessives (e.g., rare disease alleles) from drifting to high frequency, and prevents random drift of (functional) traits. In the genomics era, genomics data allow for many alternative measures of inbreeding and genomic relationships. Genomic relationships/inbreeding can be classified into (i) homozygosity/heterozygosity based (e.g., molecular kinship matrix); (ii) genetic drift-based, i.e., changes of allele frequencies; or (iii) IBD-based, i.e., SNPs are used in linkage analyses to identify IBD segments. Here, alternative measures of inbreeding/relationship were used to manage genetic diversity in genomic optimal contribution (GOC) selection schemes. Contrary to classic inbreeding theory, it was found that drift and homozygosity-based inbreeding could differ substantially in GOC schemes unless diversity management was based upon IBD. When using a homozygosity-based measure of relationship, the inbreeding management resulted in allele frequency changes toward 0.5 giving a low rate of increase in homozygosity for the panel used for management, but not for unmanaged neutral loci, at the expense of a high genetic drift. When genomic relationship matrices were based on drift, following VanRaden and as in GCTA, drift was low at the expense of a high rate of increase in homozygosity. The use of IBD-based relationship matrices for inbreeding management limited both drift and the homozygosity-based rate of inbreeding to their target values. Genetic improvement per percent of inbreeding was highest when GOC used IBD-based relationships irrespective of the inbreeding measure used. Genomic relationships based on runs of homozygosity resulted in very high initial improvement per percent of inbreeding, but also in substantial discrepancies between drift and homozygosity-based rates of inbreeding, and resulted in a drift that exceeded its target value. The discrepancy between drift and homozygosity-based rates of inbreeding was caused by a covariance between initial allele frequency and the subsequent change in frequency, which becomes stronger when using data from whole genome sequence.

Keywords: genetic diversity; genetic drift; genetic gain; genomic relationships; inbreeding; optimum contribution selection.

FIGURE 1

Histogram of the minor allele frequencies (MAF) of the SNPs in the whole genome sequence of the founder population (t = 0) observed in the simulations following 4000 generations of mutation and random selection.

FIGURE 2

The total number of selected parents for each generation for different breeding schemes. The total is the number of animals with optimal contributions >0 required to achieve a fractional increase in the OC constraint of 0.005.

FIGURE 3

The covariance between the standardized change in allele frequency at t = 20 and the standardize frequency at t = 0 for the 7000 SNP loci in Panel N for a randomly chosen replicate. Standardization is by $\sqrt{p_{0,k}(1-p_{0,k})}$ for locus k. The solid black line is the fitted linear regression y = 0.0083 + 0.0070×, with SES 0.0042 and 0.0021, respectively, and a Pearson correlation r = 0.040. For this replicate Fdrift = 0.123, Fhom = 0.178, and twice the covariance was 0.0555. The upper x-axis shows the untransformed frequency.

FIGURE 4

Changes in inbreeding coefficients Fdrift and Fhom for the neutral loci of Panel N over time plotted on a logarithmic scale where a constant rate of inbreeding results in a linear increase of over time: (A) natural logarithm of (1–F_hom); and (B) natural logarithm of (1–F_drift).

FIGURE 5

Genetic gain, Gt plotted against inbreeding for generations 1–20, where inbreeding is transformed to a logarithmic scale by –log(1-F_t) for F_hom (A) or F_drift (B). For ΔF = 0.005, the target after 20 generations is shown (–log(1-F_t) = 0.1).

FIGURE 6

The trait genetic variance of the individuals plotted over time.