Abstract
BackgroundDeleterious 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.ResultsWe 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.ConclusionsWe 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.
Highlights
Deleterious recessive conditions have been primarily studied in the context of Mendelian diseases
The concept of using routinely gathered, quantitative traits as proxies of genetic disorders is based on the idea that phenotypes such as growth or liveweight might be indicative of the overall health status of the animal, e.g. reduced growth could be caused by an underlying genetic disorder, in which case such effects could be detected via genome-wide association studies (GWAS)
GWAS for lactation traits We performed GWAS across the five milk traits of interest, namely milk volume, milk protein yield, milk fat yield, milk protein percentage, and milk fat percentage, to identify non-additive quantitative trait loci (QTL) (Fig. 1). Both additive and dominance effects are included in these plots, and the iterative analysis identified 23 dominance QTL signals that were above the false discovery rate (FDR) threshold of 1 × 10–3
Summary
Deleterious recessive conditions have been primarily studied in the context of Mendelian diseases. Non-additive genetic effects are best known from studies of Mendelian diseases, where recessive conditions have been shown to have major deleterious impacts on health and performance. It is relevant to investigate whether other measured traits might serve as proxies of animal fitness, with a view to extend the scope of this approach Lactation traits such as milk volume comprise one of the most commonly targeted classes of quantitative traits studied in cattle, where additive analyses of these traits have identified numerous candidate causative genes such as DGAT1 [13], GHR [14], ABCG2 [15], GPAT4 [16], and MGST1 [17]. We describe the discovery of several novel major effect recessive loci and highlight candidate mutations that could underlie these undiagnosed recessive disorders
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
