Mapping Quantitative Trait Loci Controlling Milk Production in Dairy Cattle by Exploiting Progeny Testing

We have exploited ``progeny testing' to map quantitative trait loci (QTL) underlying the genetic variation of milk production in a selected dairy cattle population. A total of 1,518 sires, with progeny tests based on the milking performances of > 150,000 daughters jointly, was genotyped for 159 autosomal microsatellites bracketing 1645 centimorgan or approximately two thirds of the bovine genome. Using a maximum likelihood multilocus linkage analysis accounting for variance heterogeneity of the phenotypes, we identified five chromosomes giving very strong evidence (LOD score >/= 3) for the presence of a QTL controlling milk production: chromosomes 1, 6, 9, 10 and 20. These findings demonstrate that loci with considerable effects on milk production are still segregating in highly selected populations and pave the way toward marker-assisted selection in dairy cattle breeding.     

A genome map of divergent artificial selection between Bos taurus dairy cattle and Bos taurus beef cattle

A number of cattle breeds have become highly specialized for milk or beef production, following strong artificial selection for these traits. In this paper, we compare allele frequencies from 9323 single nucleotide polymorphism (SNP) markers genotyped in dairy and beef cattle breeds averaged in sliding windows across the genome, with the aim of identifying divergently selected regions of the genome between the production types. The value of the method for identifying selection signatures was validated by four sources of evidence. First, differences in allele frequencies between dairy and beef cattle at individual SNPs were correlated with the effects of those SNPs on production traits. Secondly, large differences in allele frequencies generally occurred in the same location for two independent data sets (correlation 0.45) between sliding window averages. Thirdly, the largest differences in sliding window average difference in allele frequencies were found on chromosome 20 in the region of the growth hormone receptor gene, which carries a mutation known to have an effect on milk production traits in a number of dairy populations. Finally, for the chromosome tested, the location of selection signatures between dairy and beef cattle was correlated with the location of selection signatures within dairy cattle.     

Genetic correlations and their dependence on environmental similarity—Insights from livestock data

Genetic correlations for a trait across environments are predicted to decrease as environments diverge. However, estimates of genetic correlations from natural populations are typically defined across a limited environmental range and prone to very large standard errors, making it difficult to test this prediction. We address the importance of environmental distance on genetic correlations by employing data from domestic cattle in which abundant and accurate estimates are available from a wide range of environments. Three production traits related to milk yield show a clear decrease in genetic correlations with increasing environmental divergence. This pattern was also evident for growth traits and other yield traits but not for traits related to reproduction, morphology, physiology, or disease. We suspect that this reflects weaker selection on these latter trait classes compared to production traits, or alternatively the effects of selection are constrained by unfavorable genetic correlations between traits. The results support the notion that traits that historically have been under strong directional selection in a small range of frequently encountered environments will evolve high genetic correlations across these environments, while exposure to uncommon (and dissimilar) environments lead to a reranking of gene effects and a decrease in genetic correlations across environments.     

Genome-wide association mapping in Norwegian Red cattle identifies quantitative trait loci for fertility and milk production on BTA12

Reproductive performance is a critical trait in dairy cattle. Poor reproductive performance leads to prolonged calving intervals, higher culling rates and extra expenses related to multiple inseminations, veterinary treatments and replacements. Genetic gain for improved reproduction through traditional selection is often slow because of low heritability and negative correlations with production traits. Detection of DNA markers associated with improved reproductive performance through genome-wide association studies could lead to genetic gain that is more balanced between fertility and production. Norwegian Red cattle are well suited for such studies, as very large numbers of detailed reproduction records are available. We conducted a genome-wide association study for non-return rate, fertility treatments and retained placenta using almost 1 million records on these traits and 17 343 genome-wide single-nucleotide polymorphisms. Genotyping costs were minimized by genotyping the sires of the cows recorded and by using daughter averages as phenotypes. The genotyped sires were assigned to either a discovery or a validation population. Associations were only considered to be validated if they were significant in both groups. Strong associations were found and validated on chromosomes 1, 5, 8, 9, 11 and 12. Several of these were highly supported by findings in other studies. The most important result was an association for non-return rate in heifers in a region of BTA12 where several associations for milk production traits have previously been found. Subsequent fine-mapping verified the presence of a quantitative trait loci (QTL) having opposing effects on non-return rate and milk production at 18 Mb. The other reproduction QTL did not have pleiotropic effects on milk production, and these are therefore of considerable interest for use in marker-assisted selection.     

Associations between blood groups, blood protein polymorphisms and breeding values for production traits in Swedish Red and White Dairy bulls

The relationships of nine blood group systems and two blood protein polymorphisms with breeding values for several production traits were examined in dairy cattle of the Swedish Red and White (SRB) breed. The material consisted of 2212 bulls; the bulls were performance tested for growth rate and their breeding values for milk yield, fat and protein content in milk were estimated from progeny tests. The direct effect of marker alleles or marker phenotypes was analysed in a multiple regression model. Several significant associations were found; many supported earlier findings. However, the contribution of the markers to the total variation of the breeding values was very small. Linkage between marker loci and production loci was studied in offspring from heterozygous sires by estimating the interactions between sire and marker alle using a model eliminating the direct effects of sire and marker alle. There were strong indications of linkage between some marker loci (e.g. B, J and Am-1 loci) and loci with large effects on production traits.     

中国荷斯坦牛CVM的基因检测及其与产奶性状的关联分析

脊椎畸形综合征(Complex vertebral malformation, CVM)是由位于牛第3号染色体(BTA3)的SLC35A3基因外显子4的一个单碱基突变(G559T)所致。该致病基因在世界许多国家的荷斯坦牛群中都有一定的比例。文章对北京地区38头优秀种公牛进行分析, 发现了4头携带者, 进而检测了这些携带者公牛的555头女儿的基因型, 其中携带者占检测母牛数的44.0%。此外, 关联分析结果表明, 携带者母牛与非携带者母牛的生产性能之间存在显著差异(P<0.01)。携带者母牛的5个产奶性状育种值均显著高于非携带者, 泌乳持续力和体细胞评分SCS的育种值也比非携带者略高。CVM致病基因可能与BTA3上影响产奶性状的QTL或基因连锁。因此, 建议生产中对CVM携带者进行逐步淘汰     

A whole genome scan for QTL affecting milk protein percentage in Italian Holstein cattle, applying selective milk DNA pooling and multiple marker mapping in a daughter design

We report on a complete genome scan for quantitative trait loci (QTL) affecting milk protein percentage (PP) in the Italian Holstein-Friesian cattle population, applying a selective DNA pooling strategy in a daughter design. Ten Holstein-Friesian sires were chosen, and for each sire, about 200 daughters, each from the high and low tails of estimated breeding value for PP, were used to construct milk DNA pools. Sires and pools were genotyped for 181 dinucleotide microsatellites covering all cattle autosomes. Sire marker allele frequencies in the pools were obtained by shadow correction of peak height in the electropherograms. After quality control, pool data from eight sires were used for all subsequent analyses. The QTL heterozygosity estimate was lower than that of similar studies in other cattle populations. Multiple marker mapping identified 19 QTL located on 14 chromosomes (BTA1, 2, 3, 4, 5, 6, 8, 9, 12, 14, 17, 20, 23 and 27). The sires were also genotyped for seven polymorphic sites in six candidate genes (ABCG2, SPP1, casein kappa, DGAT1, GHR and PRLR) located within QTL regions of BTA6, 14 and 20 found in this study. The results confirmed or excluded the involvement of some of the analysed markers as the causative polymorphic sites of the identified QTL. The QTL identified, combined with genotype data of these candidate genes, will help to identify other quantitative trait genes and clarify the complex QTL patterns observed for a few chromosomes. Overall, the results are consistent with the Italian Holstein population having been under long-term selection for high PP.     

DNA markers and crossbreeding scheme as means to select sires for heterosis in egg production of chickens

Genotypes for 24 microsatellite markers, dispersed across the chicken genome, were used to predict progeny performance and heterosis for egg production (number and mass) in 'layers' (egg-type chickens). These markers were used to evaluate genetic distance between each of 39 sires sampled from two-layer male-lines; Rhode Island Red (RIR) and White egg Leghorn (Leghorn), and a DNA pool of 30 randomly sampled females from a Brown-egg female line (Silver). Each sire was analysed for egg production across months in the laying period and cumulatively in each of three subperiods; onset (2 month), mid (9 month) and late (1 month). The average Reynolds' genetic distance between Leghorn sires and the Silver female line (theta;=0.6) was significantly higher than that between RIR sires and the Silver female line (theta;=0.5). Neither performance nor heterosis values in the RIR sire's daughters were associated with genetic distance values between sires and the Silver female line. On the other hand, performance as well as heterosis values of Leghorn's daughters were positively associated with genetic distance. This association was particularly evident in the mid-subperiod. If 25% of the most genetically distant Leghorn sires from the Silver female line had been selected in a single generation on the basis of DNA markers information only, average egg production of the crossbred daughters would have been improved by about nine eggs (3%). In principle, further improvement is possible if selection to increase genetic distance between the parental lines is carried on.     

Spatio-temporal modelling of heat stress and climate change implications for the Murray dairy region,Australia

The Murray dairy region produces approximately 1.85 billion litres of milk each year, representing about 20 % of Australia’s total annual milk production. An ongoing production challenge in this region is the management of the impacts of heat stress during spring and summer. An increase in the frequency and severity of extreme temperature events due to climate change may result in additional heat stress and production losses. This paper assesses the changing nature of heat stress now, and into the future, using historical data and climate change projections for the region using the temperature humidity index (THI). Projected temperature and relative humidity changes from two global climate models (GCMs), CSIRO MK3.5 and CCR-MIROC-H, have been used to calculate THI values for 2025 and 2050, and summarized as mean occurrence of, and mean length of consecutive high heat stress periods. The future climate scenarios explored show that by 2025 an additional 12–15 days (compared to 1971 to 2000 baseline data) of moderate to severe heat stress are likely across much of the study region. By 2050, larger increases in severity and occurrence of heat stress are likely (i.e. an additional 31–42 moderate to severe heat stress days compared with baseline data). This increasing trend will have a negative impact on milk production among dairy cattle in the region. The results from this study provide useful insights on the trends in THI in the region. Dairy farmers and the dairy industry could use these results to devise and prioritise adaptation options to deal with projected increases in heat stress frequency and severity.     

Detection of Haplotypes Associated with Prenatal Death in Dairy Cattle and Identification of Deleterious Mutations in GART,SHBG and SLC37A2

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.     

Quantitative trait loci affecting lactose and total solids on chromosome 6 in Brazilian Gir dairy cattle

Fourteen Brazilian Gir sire families with 657 daughters were analyzed for quantitative trait loci (QTL) on chromosome 6 affecting lactose and total solids. Cows and sires were genotyped with 27 microsatellites with a mean spacing between markers of 4.9 cM. We used a 1% chromosome-wide threshold for QTL qualification. A QTL for lactose yield was found close to marker MNB66 in three families. A QTL for total solid yield was identified close to marker BMS2508 in three families. A QTL for lactose percentage, close to marker DIK1182, was identified in two families. A QTL for total solid percentage, close to marker MNB208, was identified in four families. These QTLs could be used for selection of animals in dairy production systems.     

Incidence of 1/29 translocation in Bolivian Creole and Brahman Yacumeño cattle

In Bolivia, four different Creole cattle breeds can be found, as well as other European and Zebu breeds adapted to local environments. The relationship between the occurrence of the 1/29 translocation and subfertility is well known, and analysis of Y chromosome morphology is useful to determine a possible introgression with Bos indicus. The incidence of the 1/29 translocation was analyzed in four Bolivian Creole cattle breeds and the Brahman Yacume?o population, as well as on four farms with phenotypical Creole-type cattle. In 259 (164 dams and 95 sires) Bolivian Creole cattle, 10.42% of the individuals demonstrated the 1/29 translocation, with a variation from 0 to 28.20% between the breeds. In contrast, 43 (19 dams and 24 sires) Yacume?o Brahman and the Creole-type cattle did not show the centric fusion. The highly significant differences between Creole cattle breeds in relation to the incidence of 1/29 translocation could be a consequence of factors such as founder group, genetic drift, and selection. The low frequency observed in the Saavedre?io Creole dairy cattle might be explained by its breeding under a more intensive system, and selection according to milk yield and fertility traits. Finally, no relation between acrocentric Y chromosomes and 1/29 translocation was observed.     

Quantitative trait locus-by-environment interaction for milk yield traits on Bos taurus autosome 6

Genotype-by-environment interactions for production traits in dairy cattle have often been observed, while QTL analyses have focused on detecting genes with general effects on production traits. In this study, a QTL search for genes with environmental interaction for the traits milk yield, protein yield, and fat yield were performed on Bos taurus autosome 6 (BTA6), also including information about the previously investigated candidate genes ABCG2 and OPN. The animals in the study were Norwegian Red. Eighteen grandsires and 716 sires were genotyped for 362 markers on BTA6. Every marker bracket was regarded as a putative QTL position. The effects of the candidate genes and the putative QTL were modeled as a regression on an environmental parameter (herd year), which is based on the predicted herd-year effect for the trait. Two QTL were found to have environmentally dependent effects on milk yield. These QTL were located 3.6 cM upstream and 9.1 cM downstream from ABCG2. No environmentally dependent QTL was found to significantly affect protein or fat yield.     

Genotype by feeding system interaction in the genetic evaluation of Jersey cattle for milk yield

Results of studies in dairy cattle about the magnitude of the genotype-environment interaction (GEI) are variable, depending on the definitions of genotype and environment. Therefore, the objective of this study was to determine the magnitude of the interaction of genotype and feeding system (confinement and grazing) in the Mexican genetic evaluation of Jersey cattle for milk yield. The number of lactations and animals in the pedigree used were 5122 and 18 432. An animal model and the MTDFREML program were used to estimate genetic parameters and predict genetic values of the animals. Bivariate analysis was carried out considering the performance of confined and grazing cows as two different traits. Three indicator variables were used to assess GEI: (i) magnitude of the genetic correlation coefficients, (ii) correlation between predicted breeding values and (iii) frequency of coincidence in the ranking of top sires. The magnitude of GEI depended on the choice of the indicator variable. The estimate of genetic correlation coefficient less than unity (0.76; P < 0.05) suggested the presence of biologically important GEI. The differences in phenotypic averages and variances between confinement and grazing systems seem to be the main causes for the genotype by environment interaction detected. However, the correlation coefficient between breeding values from confined and grazing animals (0.96) and the frequency of coincidence between breeding values of common sires within the top 100 in confinement and grazing (0.86) indicated low-to-moderate re-ranking of animals or top sires. In addition, the high correlations between predicted breeding values of Mexican genetic evaluation and the two environments (0.99 and 0.93 for confinement and grazing) indicated that for the two feeding systems, breeding values from national analyses could be safely used.     

Genome‐wide association mapping and pathway analysis of leukosis incidence in a US Holstein cattle population

Bovine leukosis virus is an oncogenic virus that infects B cells, causing bovine leukosis disease. This disease is known to have a negative impact on dairy cattle production and, because no treatment or vaccine is available, finding a possible genetic solution is important. Our objective was to perform a comprehensive genetic analysis of leukosis incidence in dairy cattle. Data on leukosis occurrence, pedigree and molecular information were combined into multitrait GBLUP models with milk yield (MY) and somatic cell score (SCS) to estimate genetic parameters and to perform whole‐genome scans and pathway analysis. Leukosis data were available for 11 554 Holsteins daughters of 3002 sires from 112 herds in 16 US states. Genotypes from a 60K SNP panel were available for 961 of those bulls as well as for 2039 additional bulls. Heritability for leukosis incidence was estimated at about 8%, and the genetic correlations of leukosis disease incidence with MY and SCS were moderate at 0.18 and 0.20 respectively. The genome‐wide scan indicated that leukosis is a complex trait, possibly modulated by many genes. The gene set analysis identified many functional terms that showed significant enrichment of genes associated with leukosis. Many of these terms, such as G‐Protein Coupled Receptor Signaling Pathway, Regulation of Nucleotide Metabolic Process and different calcium‐related processes, are known to be related to retrovirus infection. Overall, our findings contribute to a better understanding of the genetic architecture of this complex disease. The functional categories associated with leukosis may be useful in future studies on fine mapping of genes and development of dairy cattle breeding strategies.     

Applications of sexed semen in cattle production

Sexed semen will contribute to increased profitability of dairy and beef cattle production in a variety of ways. It could be used to produce offspring of the desired sex from a particular mating to take advantage of differences in value of males and females for specific marketing purposes. Commercial dairy farmers, those who produce and market milk, could use sexed semen to produce replacement daughters from genetically superior cows and beef crossbred sons from the remainder of their cow population. To increase the rate of response to selection, seedstock dairy cattle breeders could produce bulls for progeny testing from a smaller number of elite dams by using sexed semen to ensure that all of them produced a son. Using sexed semen could then reduce the cost of progeny testing those bulls, because fewer matings would be necessary to produce any required number of daughters. Commercial beef cattle farmers, producing animals for eventual slaughter, could use sexed semen to capitalize on the higher value of male than female offspring for meat production. They could also use sexed semen to produce specialized, genetically superior replacement heifers from as small a proportion of the herd as possible. This would allow the remainder of the herd to produce male calves from bulls or breeds with superior genetic merit for growth, feed conversion efficiency, and carcass merit. Single-sex, bred-heifer systems, in which each female is sold for slaughter soon after weaning her replacement daughter, would be possible with the use of X-chromosome-sorted semen. Use of sexed semen would make terminal crossbreeding systems more efficient and sustainable in beef cattle. Fewer females would be required to produce specialized maternal crossbred daughters, and more could be devoted to producing highly efficient, terminal crossbred sons.     

Quantitative trait locus mapping in dairy cattle by means of selective milk DNA pooling using dinucleotide microsatellite markers: analysis of milk protein percentage.

"Selective DNA pooling" accomplishes quantitative trait locus (QTL) mapping through densitometric estimates of marker allele frequencies in pooled DNA samples of phenotypically extreme individuals. With poly(TG) microsatellites, such estimates are confounded by "shadow" ("stutter") bands. A correction procedure was developed on the basis of an observed linear regression between shadow band intensity and allele TG repeat number. Using this procedure, a selective DNA pooling study with respect to milk protein percentage was implemented in Israel-Holstein dairy cattle. Pools were prepared from milk samples of high and low daughters of each of seven sires and genotyped with respect to 11 markers. Highly significant associations with milk protein percentage were found for 5 of the markers; 4 of these markers confirmed previous reports. Selective DNA pooling accessed 80.6 and 48.3%, respectively, of the information that would have been available through individual selective genotyping or total population genotyping. In effect, the statistical power of 45,600 individual genotypings was obtained from 328 pool genotypings. This methodology can make genome-wide mapping of QTL accessible to moderately sized breeding organizations.     

Impact of bovine somatotropin on ranking for genetic value of dairy sires for milk yield traits and somatic cell score

Records of Holstein cows were used to examine how different models account for the effect of bovine somatotropin (bST) treatment on genetic evaluation of dairy sires for yield traits and somatic cell score. Data set 1 included 65,720 first-lactation records. Set 2 included 50,644 second-lactation records. Set 3 included 45,505 records for lactations three, four and five. Estimated breeding values (EBV) of sires were with three different animal models. With Model 1, bST administration was ignored. With Model 2, bST administration was used as a fixed effect. With Model 3, administration of bST was used to define the contemporary group (herd-year-month of calving-bST). Correlations for EBV of 1,366 sires with treated daughters between pairs of the three models were calculated for milk, fat and protein yields and somatic cell score for the three data sets. Correlations for EBV of sires between pairs of models for all traits ranged from 0.971 to 0.999. Fractions of sires with bST-treated progeny selected in common (top 10 to 15%) were 0.94 and usually greater for all pairs of models for all traits and parities. For this study, the method of statistical adjustment for bST treatment resulted in a negligible effect on genetic evaluations of sires when some daughters were treated with bST and suggests that selection of sires to produce the next generation of sires and cows might not be significantly affected by how the effect of bST is modeled for prediction of breeding values for milk, fat and protein yields and somatic cell score.     

Prospects for improving reproductive performance through genetic selection

Prospects for improving female fertility in dairy cattle using genetic selection are reviewed. Today's high producing cows have shorter estrous cycles, fewer standing events, shorter duration of estrus, and more frequent multiple ovulations. Although high milk production is often implicated as the cause of impaired fertility, the impact of inadequate body condition appears to be greater, as the latter has a significant impact on probability of conception, rate of embryonic loss, and proportion of anestrous animals. Genetic improvement of female fertility can be achieved by indirect selection for longevity or body condition score, or by direct selection for traits such as daughter pregnancy rate. Most leading dairy countries have implemented genetic evaluation systems for female fertility in the past decade, but refinement of these systems to account for hormonal synchronization, differences in the voluntary waiting period, exposure to natural service bulls, and other confounding factors is warranted. Recent work has focused on the development of data collection and genetic evaluation systems that will allow selection of bulls that have daughters that are resistant to common health disorders, including mastitis, lameness, ketosis, displaced abomasum, and metritis. Such systems will allow selection of animals that can remain healthy and fertile while producing large quantities of milk.     

Imputation of missing genotypes from low‐ to high‐density SNP panel in different population designs

Imputation of missing genotypes, in particular from low density to high density, is an important issue in genomic selection and genome‐wide association studies. Given the marker densities, the most important factors affecting imputation accuracy are the size of the reference population and the relationship between individuals in the reference (genotyped with high‐density panel) and study (genotyped with low‐density panel) populations. In this study, we investigated the imputation accuracies when the reference population (genotyped with Illumina BovineSNP50 SNP panel) contained sires, halfsibs, or both sires and halfsibs of the individuals in the study population (genotyped with Illumina BovineLD SNP panel) using three imputation programs (fimpute v2.2, findhap v2, and beagle v3.3.2). Two criteria, correlation between true and imputed genotypes and missing rate after imputation, were used to evaluate the performance of the three programs in different scenarios. Our results showed that fimpute performed the best in all cases, with correlations from 0.921 to 0.978 when imputing from sires to their daughters or between halfsibs. In general, the accuracies of imputing between halfsibs or from sires to their daughters were higher than were those imputing between non‐halfsibs or from sires to non‐daughters. Including both sires and halfsibs in the reference population did not improve the imputation performance in comparison with when only including halfsibs in the reference population for all the three programs.