Evaluating the potential impact of selection for the A2 milk allele on inbreeding and performance in Australian Holstein cattle

Selection decisions are generally based on estimated breeding values (EBV) for a combination of traits that are polygenic (e.g. milk production). However, in some cases, there is additional intense selection for a single allele, or SNP, for a perceived benefit, such as selection for polled or A2 milk. Using a dataset where the A2 mutation was imputed using a reference population with whole genome sequence, we tested the hypothesis that intense selection in Australian Holstein cattle for the A2 allele in the β-casein gene may have resulted in increased inbreeding. We also estimated the average difference in performance between animals homozygous for the A1 or A2 allele for a range of traits. Using high-density genotypes we compared differences in genome-wide and regional inbreeding between Holstein cows homozygous for either the A1 or A2 β-casein alleles i.e. A1/A1 or A2/A2. This study shows that between the years 2000 to 2017, the frequency of the A2/A2 genotype increased by 20% in Holstein cows (from 32% to 52%). Our results suggest that selection for homozygosity at the β-casein A2 allele has increased inbreeding both across the genome and on chromosome 6 in A2/A2 Holstein cows. Animals that were A2/A2 were twice as likely to have a run of homozygosity of at least 1Mb long across the β-casein locus compared to animals that were A1/A1. Cows that are homozygous for the A2 allele had an average protein yield EBV advantage of 0.24 genetic standard deviations (SD) compared to A1/A1 homozygous cows. In contrast, A2/A2 homozygous animals were on average 0.2 genetic SD inferior on fertility EBV. As a result, the difference in the overall economic index (that includes traits contributing to profitability) there was only a small advantage of 0.05 SD for A2/A2 cows compared to A1/A1 cows. However, strong selection for the A2 allele has likely led to a higher level of regional and overall inbreeding which in the long term could harm genetic progress for some or all economic traits. Therefore, applying approaches that mitigate rapid inbreeding while selecting for preferred alleles and quantitative traits may be desirable.