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Milk is composed of a complex mixture of lipids, proteins, carbohydrates and various vitamins and minerals as a source of nutrition for young mammals. The composition of milk varies between individuals, with lipid composition in particular being highly heritable. Recent reports have highlighted a region of bovine chromosome 27 harbouring variants affecting milk fat percentage and fatty acid content. We aimed to further investigate this locus in two independent cattle populations, consisting of a Holstein-Friesian x Jersey crossbreed pedigree of 711 F2 cows, and a collection of 32,530 mixed ancestry Bos taurus cows. Bayesian genome-wide association mapping using markers imputed from the Illumina BovineHD chip revealed a large quantitative trait locus (QTL) for milk fat percentage on chromosome 27, present in both populations. We also investigated a range of other milk composition phenotypes, and report additional associations at this locus for fat yield, protein percentage and yield, lactose percentage and yield, milk volume, and the proportions of numerous milk fatty acids. We then used mammary RNA sequence data from 212 lactating cows to assess the transcript abundance of genes located in the milk fat percentage QTL interval. This analysis revealed a strong eQTL for AGPAT6, demonstrating that high milk fat percentage genotype is also additively associated with increased expression of the AGPAT6 gene. Finally, we used whole genome sequence data from six F1 sires to target a panel of novel AGPAT6 locus variants for genotyping in the F2 crossbreed population. Association analysis of 58 of these variants revealed highly significant association for polymorphisms mapping to the 5'UTR exons and intron 1 of AGPAT6. Taken together, these data suggest that variants affecting the expression of AGPAT6 are causally involved in differential milk fat synthesis, with pleiotropic consequences for a diverse range of other milk components.

Aim: To estimate genetic and crossbreeding parameters for the incidence of recorded clinical lameness in New Zealand dairy cattle., Methods: Herd records from 76,357 cows, collected during the 2005/06 to 2008/09 milking seasons from 155 herds in the Livestock Improvement Corporation young sire progeny test scheme, were used to estimate genetic parameters and breed effects for incidence of recorded clinical lameness in HolsteinFriesian, Jersey and crossbred dairy cattle. Recorded clinical lameness was coded "1" for cows that presented at least one event of clinical lameness at any day during the season and "0" for unaffected cows. Genetic parameters were estimated using an animal model across breeds considering all and then only first lactation records. Heritability and repeatability of recorded clinical lameness were calculated from the variance component estimates both with and without logit transformation., Results: The mean incidence of recorded clinical lameness per herd was 6.3 (min 2, max 34)%. The incidence of recorded clinical lameness in Holstein Friesian cows (mean 6.8, SE 0.24%) was higher than the incidence of recorded clinical lameness in crossbred (mean 6.1, SE 0.19%) and Jersey cows (mean 6.0, SE 0.28%) (p=0.0002). There was no difference in incidence between crossbred and Jersey cows (p=0.96). Estimates of the heritability of recorded clinical lameness as an untransformed trait were 0.053 (SE 0.014) for first lactation records and 0.016 (SE 0.003) for all lactation records. As a transformed (logit) trait heritabilities were 0.067 (SE 0.024) and 0.044 (SE 0.016) for first and all lactation records, respectively. The repeatability estimates of recorded clinical lameness were 0.071 (SE 0.005) and 0.107 (SE 0.011) for untransformed and logit transformed lactation records, respectively. Sire estimated breeding values for recorded clinical lameness showed the lowest values in Jersey sires, and ranged between -5 and 8%., Conclusions: Despite the low heritability of recorded clinical lameness, this study provided evidence that there is significant exploitable animal genetic variation. Selection of specific sires across and within breeds could be an option for increasing genetic resistance to lameness in New Zealand dairy cattle.

We report mapping of a quantitative trait locus (QTL) with a major effect on bovine stature to a ∼780-kb interval using a Hidden Markov Model-based approach that simultaneously exploits linkage and linkage disequilibrium. We re-sequenced the interval in six sires with known QTL genotype and identified 13 clustered candidate quantitative trait nucleotides (QTNs) out of >9,572 discovered variants. We eliminated five candidate QTNs by studying the phenotypic effect of a recombinant haplotype identified in a breed diversity panel. We show that the QTL influences fetal expression of seven of the nine genes mapping to the ∼780-kb interval. We further show that two of the eight candidate QTNs, mapping to the PLAG1-CHCHD7 intergenic region, influence bidirectional promoter strength and affect binding of nuclear factors. By performing expression QTL analyses, we identified a splice site variant in CHCHD7 and exploited this naturally occurring null allele to exclude CHCHD7 as single causative gene.

Aim: To identify quantitative trait loci (QTL) affecting the concentration of beta-lactoglobulin in milk, and to evaluate the effect of beta-lactoglobulin genetic variants on the concentration of fat, protein and casein in bovine milk., Methods: A herd of 850 F2 Holstein-Friesian x Jersey crossbred cows was produced through mating six Holstein-Friesian x Jersey F1 bulls of high genetic merit with F1 cows from the national herd. A total of 1,610 herd-test records from 556 second-parity crossbreds were analysed. The concentration of fat, protein and casein in milk was measured at peak, mid- and late lactation, during the production seasons of 2003-2004 and 2004-2005. Liveweight was measured daily. DNA from the F2 animals, their F1 dams and sires, and selected grandsires was genotyped across the genome, initially with 285 microsatellite markers, and subsequently with 6,634 single nucleotide polymorphisms (SNP)., Results: A highly significant QTL for the concentration of beta-lactoglobulin in milk was identified, which coincided with the position of the beta-lactoglobulin gene on bovine Chromosome 11. No other consistently significant QTL for the concentration of beta-lactoglobulin in milk were detected. Cows with the BB beta-lactoglobulin genotype produced milk with a 30% lower concentration of beta-lactoglobulin than cows with the AA genotype. The beta-lactoglobulin polymorphism also explained variation in the proportion of casein in total protein. In addition, the percentage of fat was higher for BB than AA animals, whereas the percentage of total protein, mean daily milk yield and liveweight did not differ between AA and BB animals., Conclusions: A significant QTL determining the concentration of beta-lactoglobulin in milk was identified. Selection of animals for the beta-lactoglobulin B-allele may enable the production of milk naturally enriched for casein, thus allowing a potential increase in the yield of cheese. There may be additional future value in production of bovine milk more like human milk, where decreasing the concentration of beta-lactoglobulin is desirable.

The imprints of domestication and breed development on the genomes of livestock likely differ from those of companion animals. A deep draft sequence assembly of shotgun reads from a single Hereford female and comparative sequences sampled from six additional breeds were used to develop probes to interrogate 37,470 single-nucleotide polymorphisms (SNPs) in 497 cattle from 19 geographically and biologically diverse breeds. These data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation. Domestication and artificial selection appear to have left detectable signatures of selection within the cattle genome, yet the current levels of diversity within breeds are at least as great as exists within humans.