Stature is affected by many polymorphisms of small effect in humans . In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 × 10) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP-seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals.

The regular decrease of female fertility over time is a major concern in modern dairy cattle industry. Only half of this decrease is explained by indirect response to selection on milk production, suggesting the existence of other factors such as embryonic lethal genetic defects. Genomic regions harboring recessive deleterious mutations were detected in three dairy cattle breeds by identifying frequent haplotypes (>1%) showing a deficit in homozygotes among Illumina Bovine 50k Beadchip haplotyping data from the French genomic selection database (47,878 Holstein, 16,833 Montbéliarde, and 11,466 Normande animals). Thirty-four candidate haplotypes (p<10−4) including previously reported regions associated with Brachyspina, CVM, HH1, and HH3 in Holstein breed were identified. Haplotype length varied from 1 to 4.8 Mb and frequencies from 1.7 up to 9%. A significant negative effect on calving rate, consistent in heifers and in lactating cows, was observed for 9 of these haplotypes in matings between carrier bulls and daughters of carrier sires, confirming their association with embryonic lethal mutations. Eight regions were further investigated using whole genome sequencing data from heterozygous bull carriers and control animals (45 animals in total). Six strong candidate causative mutations including polymorphisms previously reported in FANCI (Brachyspina), SLC35A3 (CVM), APAF1 (HH1) and three novel mutations with very damaging effect on the protein structure, according to SIFT and Polyphen-2, were detected in GART, SHBG and SLC37A2 genes. In conclusion, this study reveals a yet hidden consequence of the important inbreeding rate observed in intensively selected and specialized cattle breeds. Counter-selection of these mutations and management of matings will have positive consequences on female fertility in dairy cattle.

Breed differences and nonadditive genetic effects for milk production traits, somatic cell score (SCS), conception rate (CR), and days to first service (DFS) were estimated for Holstein × Montbéliarde and Holstein × Normande crossbreds, using an animal model adapted from the French genetic evaluation and extended to across-breed analysis. Inbreeding and breed differences were estimated from all purebred recorded cows. Only records from 1,137 herds with Holstein × Montbéliarde crossbred cows and from 1,033 herds with Holstein × Normande crossbred cows were used to estimate crossbreeding parameters. In these herds, crossbred cows represented about 13% of the total number of recorded animals compared with <1% when all herds were considered. Compared with the Montbéliarde and Normande breeds, the Holstein breed was genetically superior for production [+951kg and +2,444kg for 305-d mature-equivalent (305ME) milk, +40kg and +102kg for 305ME fat, +17kg and +54kg for 305ME protein, respectively] and inferior for fertility traits (-12 and -9% for CR, respectively). Inbreeding depression caused loss of yield for production traits (from -32 to -41kg of 305ME milk, -1.4 to -1.7kg of 305ME fat, and -1.1 to -1.3kg of 305ME protein per inbreeding percentage), a small increase in SCS (+0.001 to 0.006) and DFS (+0.12d), and a decrease in CR (-0.27 to -0.44%). Favorable heterosis effects were found for all traits (+494 to 524kg of 305ME milk, +21 to 22kg of 305ME fat, +15 to 16kg of 305ME protein, -0.05 to -0.04 SCS, +2 to 3% for CR, and -3 to 6d of DFS), to such a point that F1 crossbreds could compete with Holstein cows for milk production while having a better fertility. However, recombination losses suggested that some F1 heterosis was lost for backcross cows.