Background Deleterious recessive conditions have been primarily studied in the context of Mendelian diseases. Recently, several deleterious recessive mutations with large effects were discovered via non-additive genome-wide association studies (GWAS) of quantitative growth and developmental traits in cattle, which showed that quantitative traits can be used as proxies of genetic disorders when such traits are indicative of whole-animal health status. We reasoned that lactation traits in cattle might also reflect genetic disorders, given the increased energy demands of lactation and the substantial stresses imposed on the animal. In this study, we screened more than 124,000 cows for recessive effects based on lactation traits. Results We discovered five novel quantitative trait loci (QTL) that are associated with large recessive impacts on three milk yield traits, with these loci presenting missense variants in the DOCK8 , IL4R , KIAA0556 , and SLC25A4 genes or premature stop variants in the ITGAL , LRCH4 , and RBM34 genes, as candidate causal mutations. For two milk composition traits, we identified several previously reported additive QTL that display small dominance effects. By contrasting results from milk yield and milk composition phenotypes, we note differing genetic architectures. Compared to milk composition phenotypes, milk yield phenotypes had lower heritabilities and were associated with fewer additive QTL but had a higher non-additive genetic variance and were associated with a higher proportion of loci exhibiting dominance. Conclusions We identified large-effect recessive QTL which are segregating at surprisingly high frequencies in cattle. We speculate that the differences in genetic architecture between milk yield and milk composition phenotypes derive from underlying dissimilarities in the cellular and molecular representation of these traits, with yield phenotypes acting as a better proxy of underlying biological disorders through presentation of a larger number of major recessive impacts.

Abstract Background Meiotic recombination plays an important role in reproduction and evolution. The individual global recombination rate (GRR), measured as the number of crossovers (CO) per gametes, is a complex trait that has been shown to be heritable. The sex chromosomes play an important role in reproduction and fertility related traits. Therefore, variants present on the X-chromosome might have a high contribution to the genetic variation of GRR that is related to meiosis and to reproduction. Results We herein used genotyping data from 58,474 New Zealand dairy cattle to estimate the contribution of the X-chromosome to male and female GRR levels. Based on the pedigree-based relationships, we first estimated that the X-chromosome accounted for 30% of the total additive genetic variance for male GRR. This percentage was equal to 19.9% when the estimation relied on a SNP-BLUP approach assuming each SNP has a small contribution. We then carried out a haplotype-based association study to map X-linked QTL, and subsequently fine-mapped the identified QTL with imputed sequence variants. With this approach we identified three QTL with large effect accounting for 7.7% of the additive genetic variance of male GRR. The associated effects were equal to + 0.79, − 1.16 and + 1.18 CO for the alternate alleles. In females, the estimated contribution of the X-chromosome to GRR was null and no significant association with X-linked loci was found. Interestingly, two of the male GRR QTL were associated with candidate genes preferentially expressed in testis, in agreement with a male-specific effect. Finally, the most significant QTL was associated with PPP4R3C, further supporting the important role of protein phosphatase in double-strand break repair by homologous recombination. Conclusions Our study illustrates the important role the X-chromosome can have on traits such as individual recombination rate, associated with testis in males. We also show that contribution of the X-chromosome to such a trait might be sex dependent.