Inbreeding depression for litter size in two mice lines under divergent selection for environmental birth weight variability using genomic data

Abstract

Inbreeding depression (ID) is usually observed as reduced survival and fertility and may have a variable impact in different populations. The aim of this study was to estimate ID from genomic and pedigree data in the litter size (LS) of the high variability (H-Line) and the low variability (L-Line) mice lines divergently selected for environmental birth weight variability. Of these, the L-Line performed better on traits related to robustness. A total of 1587 females from 26 selection generations were genotyped with a high-density SNP array. LS data of 732 L-Line and 648 of H-Line animals were used. The following were calculated: pedigree inbreeding coefficient (FPED), genomic inbreeding derived from different genomic matrices (FNEJ, FL&H,FVR1, FVR2, and FYAN), from runs of homozygosity (FROH) and from homozygosity by descent probabilities (FHBD). FROH were calculated in the 19 autosomes (CHR). FROH and FHBD were divided into nine lengths and age classes, respectively. All the inbreeding coefficients were standardized by the mean inbreeding coefficient of the 1st generation. Regression coefficients (m) obtained from genomic data were between −3.71 with FVR2 and −5.09 with FHBD in the H-Line, and that estimated from FPED was −5.67. In the L-Line the m obtained from genomic data were between −3.52 with FVR2 and −4.55 with FHBD, and that obtained with FPED was −4.08. Significant ID effects were detected in CHR13 in the H-Line and CHR1 and CHR9 in the L-Line. The m negative trended to be lower as the ROH length increased. The age of the homozygosity by descent segment performed differently in each line, for example FHBD raised 128 generations ago produced a significant positive effect only in the L-Line. The effect of global inbreeding coefficients on the LS was negative in both lines with a higher impact in the H-Line than in the L-Line, suggesting the L-Line having higher robustness. CHR 1, 9, and 13 were candidates for future gene search. In general, more recent FROH and FHBD presented negative effects on LS while older FROH and FHBD presented positive effects on LS in both selected lines.

Lay Summary: Inbreeding has been defined as the probability that two alleles at any given locus are identical by descent, i.e., both come from a common ancestor. The reduction of fitness in a population due to the levels of inbreeding is known as inbreeding depression (ID). As a result of an experiment of divergent selection for environmental birth weight variability in mice two lines were created: high variability line (H-Line) and low variability line (L-Line). The L-Line outperformed the H-Line in traits related to animal welfare and robustness. In this study we analyzed the impact of inbreeding on the litter size to determine whether there was an ID and whether this ID differently affected the selected lines using pedigree and molecular information. The results obtained suggested that the L-Line presented lower ID. Moreover, the impact of using some molecular inbreeding coefficients was different between lines, despite the same mating restrictions were followed across generations in both lines. These findings could be related to the higher robustness observed in the L-Line.