Inference of population structure of purebred dairy and beef cattle using high-density genotype data.

Information on the genetic diversity and population structure of cattle breeds is useful when deciding the most optimal, for example, crossbreeding strategies to improve phenotypic performance by exploiting heterosis. The present study investigated the genetic diversity and population structure of the most prominent dairy and beef breeds used in Ireland. Illumina high-density genotypes (777 962 single nucleotide polymorphisms; SNPs) were available on 4623 purebred bulls from nine breeds; Angus (n=430), Belgian Blue (n=298), Charolais (n=893), Hereford (n=327), Holstein-Friesian (n=1261), Jersey (n=75), Limousin (n=943), Montbéliarde (n=33) and Simmental (n=363). Principal component analysis revealed that Angus, Hereford, and Jersey formed non-overlapping clusters, representing distinct populations. In contrast, overlapping clusters suggested geographical proximity of origin and genetic similarity between Limousin, Simmental and Montbéliarde and to a lesser extent between Holstein, Friesian and Belgian Blue. The observed SNP heterozygosity averaged across all loci was 0.379. The Belgian Blue had the greatest mean observed heterozygosity (HO=0.389) among individuals within breed while the Holstein-Friesian and Jersey populations had the lowest mean heterozygosity (HO=0.370 and 0.376, respectively). The correlation between the genomic-based and pedigree-based inbreeding coefficients was weak (r=0.171; P<0.001). Mean genomic inbreeding estimates were greatest for Jersey (0.173) and least for Hereford (0.051). The pair-wise breed fixation index (F st) ranged from 0.049 (Limousin and Charolais) to 0.165 (Hereford and Jersey). In conclusion, substantial genetic variation exists among breeds commercially used in Ireland. Thus custom-mating strategies would be successful in maximising the exploitation of heterosis in crossbreeding strategies.

Ultra-low-density genotype panels for breed assignment of Angus and Hereford cattle.

Angus and Hereford beef is marketed internationally for apparent superior meat quality attributes; DNA-based breed authenticity could be a useful instrument to ensure consumer confidence on premium meat products. The objective of this study was to develop an ultra-low-density genotype panel to accurately quantify the Angus and Hereford breed proportion in biological samples. Medium-density genotypes (13 306 single nucleotide polymorphisms (SNPs)) were available on 54 703 commercial and 4042 purebred animals. The breed proportion of the commercial animals was generated from the medium-density genotypes and this estimate was regarded as the gold-standard breed composition. Ten genotype panels (100 to 1000 SNPs) were developed from the medium-density genotypes; five methods were used to identify the most informative SNPs and these included the Delta statistic, the fixation (F st) statistic and an index of both. Breed assignment analyses were undertaken for each breed, panel density and SNP selection method separately with a programme to infer population structure using the entire 13 306 SNP panel (representing the gold-standard measure). Breed assignment was undertaken for all commercial animals (n=54 703), animals deemed to contain some proportion of Angus based on pedigree (n=5740) and animals deemed to contain some proportion of Hereford based on pedigree (n=5187). The predicted breed proportion of all animals from the lower density panels was then compared with the gold-standard breed prediction. Panel density, SNP selection method and breed all had a significant effect on the correlation of predicted and actual breed proportion. Regardless of breed, the Index method of SNP selection numerically (but not significantly) outperformed all other selection methods in accuracy (i.e. correlation and root mean square of prediction) when panel density was ⩾300 SNPs. The correlation between actual and predicted breed proportion increased as panel density increased. Using 300 SNPs (selected using the global index method), the correlation between predicted and actual breed proportion was 0.993 and 0.995 in the Angus and Hereford validation populations, respectively. When SNP panels optimised for breed prediction in one population were used to predict the breed proportion of a separate population, the correlation between predicted and actual breed proportion was 0.034 and 0.044 weaker in the Hereford and Angus populations, respectively (using the 300 SNP panel). It is necessary to include at least 300 to 400 SNPs (per breed) on genotype panels to accurately predict breed proportion from biological samples.

Evaluation of developed low-density genotype panels for imputation to higher density in independent dairy and beef cattle populations.

The objective of this study was to develop, using alternative algorithms, low-density SNP genotyping panels (384 to 12,000 SNP), which can be accurately imputed to higher-density panels across independent cattle populations. Single nucleotide polymorphisms were selected based on genomic characteristics (i.e., linkage disequilibrium [LD], minor allele frequency [MAF], and genomic distance) in a population of 1,267 Holstein-Friesian animals genotyped on the Illumina Bovine50 Beadchip (54,001 SNP). Single nucleotide polymorphism selection methods included 1) random; 2) equidistant location; 3) combination of SNP MAF and LD structure while maintaining relatively equal genomic distance between adjacent SNP; 4) a combination of high MAF, genomic distance between selected and candidate SNP, and correlation between genotypes of selected and candidate SNP; and 5) a machine learning algorithm. The panels were validated separately in 1) a population of 750 Holstein-Friesian animals with masked genotypes to reflect the lower-density SNP densities under investigation (1,249 animals with complete genotypes included in reference population) and 2) a population of 359 Limousin and Charolais cattle with high (777,962 SNP)-density genotypes (1,918 animals with complete genotypes included in the reference population). Irrespective of SNP selection method, imputation accuracy in both populations improved at a diminishing rate as the number of SNP included in the lower-density genotype panel increased. Additionally, the variability in mean imputation accuracy per individual decreased as the panel density increased. The SNP selection method had a major impact on the mean allele concordance rate, although its impact diminished as the panel density increased. Imputation accuracy for SNP selected using a combination of high SNP MAF, LD structure, and relatively equal genomic distance between SNP outperformed all other selection methods in densities < 12,000 SNP. Using this method of SNP selection, the correlation between the imputed and actual genotypes for the 3,000 SNP panel was 0.90 and 0.96 when applied to the beef and dairy populations, respectively; the respective correlations for the 6,000 SNP panel were 0.95 and 0.98. It is necessary to include between 3,000 and 6,000 SNP in a low-density panel to achieve adequate imputation accuracy to either medium density (approximately 50,000 SNP in the dairy population) or high density (approximately 700,000 SNP in the beef population) across diverse and independent populations.

Imputation of ungenotyped parental genotypes in dairy and beef cattle from progeny genotypes.

The objective of this study was to quantify the accuracy of imputing the genotype of parents using information on the genotype of their progeny and a family-based and population-based imputation algorithm. Two separate data sets were used, one containing both dairy and beef animals (n=3122) with high-density genotypes (735 151 single nucleotide polymorphisms (SNPs)) and the other containing just dairy animals (n=5489) with medium-density genotypes (51 602 SNPs). Imputation accuracy of three different genotype density panels were evaluated representing low (i.e. 6501 SNPs), medium and high density. The full genotypes of sires with genotyped half-sib progeny were masked and subsequently imputed. Genotyped half-sib progeny group sizes were altered from 4 up to 12 and the impact on imputation accuracy was quantified. Up to 157 and 258 sires were used to test the accuracy of imputation in the dairy plus beef data set and the dairy-only data set, respectively. The efficiency and accuracy of imputation was quantified as the proportion of genotypes that could not be imputed, and as both the genotype concordance rate and allele concordance rate. The median proportion of genotypes per animal that could not be imputed in the imputation process decreased as the number of genotyped half-sib progeny increased; values for the medium-density panel ranged from a median of 0.015 with a half-sib progeny group size of 4 to a median of 0.0014 to 0.0015 with a half-sib progeny group size of 8. The accuracy of imputation across different paternal half-sib progeny group sizes was similar in both data sets. Concordance rates increased considerably as the number of genotyped half-sib progeny increased from four (mean animal allele concordance rate of 0.94 in both data sets for the medium-density genotype panel) to five (mean animal allele concordance rate of 0.96 in both data sets for the medium-density genotype panel) after which it was relatively stable up to a half-sib progeny group size of eight. In the data set with dairy-only animals, sufficient sires with paternal half-sib progeny groups up to 12 were available and the within-animal mean genotype concordance rates continued to increase up to this group size. The accuracy of imputation was worst for the low-density genotypes, especially with smaller half-sib progeny group sizes but the difference in imputation accuracy between density panels diminished as progeny group size increased; the difference between high and medium-density genotype panels was relatively small across all half-sib progeny group sizes. Where biological material or genotypes are not available on individual animals, at least five progeny can be genotyped (on either a medium or high-density genotyping platform) and the parental alleles imputed with, on average, ⩾96% accuracy.

Genome-wide association study for calving traits in Holstein-Friesian dairy cattle.

Dystocia and perinatal mortality are quantitative traits that significantly impact animal productivity and welfare. Their economic importance is reflected by their inclusion in the national breeding goals of many cattle populations. The genetic architecture that influences these traits, however, has still yet to be thoroughly defined. Regions of the bovine genome associated with calving difficulty (direct and maternal) and perinatal mortality were detected in this study using a Bayesian approach with 43 204 single nucleotide polymorphisms (SNPs) on up to 1970 Holstein-Friesian bulls. Several SNPs on chromosomes 5, 6, 11, 12, 17,18 and 28 were detected to be strongly associated with these calving performance traits. Novel genomic regions with previously reported associations with growth, stature, birth weight and bone morphology were identified in the present study as being associated with the three calving performance traits. Morphological abnormalities are a known contributor to perinatal mortality and the most significantly associated SNP for perinatal mortality in the present study was located in a region in linkage disequilibrium with the gene SLC26A7. This gene, SLC26A7, has similarities and colocalises with SLC4A2, which has previously been associated with osteoporosis and mortality in cattle populations. The HHIP gene that is known to be associated with stature in humans was strongly associated with direct calving difficulty in the present study; large calves are known to, on average, have a greater likelihood of dystocia. A stemloop microRNA, bta-mir-1256, on chromosome 12, involved in post-transcriptional regulation of gene expression was associated with maternal calving difficulty. Previously reported quantitative trait loci associated with calving performance traits in other populations were again identified in this study; with one genomic region on chromosome 18 supporting very strong evidence of an underlying causative mutation and accounting for 2.1% of the genetic variation in direct calving difficulty. Overlapping genomic regions associated with one or more of the calving traits were also detected substantiating the known genetic covariances existing between these traits. Moreover, some genomic regions were only associated with one of the calving traits implying the selective genomic breeding programs exploiting these regions could help resolve genetic antagonisms.

Evidence of genetic and maternal effects on secondary sex ratio in cattle.

There is a paucity of estimates of genetic variation for secondary sex ratio (i.e., sex ratio at birth) in dairy cattle. The objective of this study was to estimate the direct and maternal genetic variance as well as maternal permanent environmental variance for offspring sex in dairy herds. The data consisted of 77,508 births from 61,963 dams and 2,859 sires in 1,369 Irish dairy herds across the years 2003 to 2008, inclusive. Mixed models were used to estimate all parameters. Significant genetic variation in sex ratio existed, with a heritability for secondary sex ratio estimated at 0.02; the genetic standard deviation was 0.07 percentage units. No maternal genetic effects on secondary sex ratio were identified but the proportion of phenotypic variance in secondary sex ratio attributable to maternal permanent environmental effects was similar to that attributable to the additive genetic variance (i.e., 0.02). These results, therefore, suggest that the paternal (genetic) influence on secondary sex ratio is just as large as the maternal (non-genetic) influence, both of which are biologically substantial. The results from this study will be useful in generating a sample population of divergent animals for inclusion in a controlled experiment to elucidate the physiological mechanism underpinning differences in secondary sex ratio.

Imputation of genotypes from low- to high-density genotyping platforms and implications for genomic selection.

The objective of this study was to quantify the accuracy achievable from imputing genotypes from a commercially available low-density marker panel (2730 single nucleotide polymorphisms (SNPs) following edits) to a commercially available higher density marker panel (51 602 SNPs following edits) in Holstein-Friesian cattle using Beagle, a freely available software package. A population of 764 Holstein-Friesian animals born since 2006 were used as the test group to quantify the accuracy of imputation, all of which had genotypes for the high-density panel; only SNPs on the low-density panel were retained with the remaining SNPs to be imputed. The reference population for imputation consisted of 4732 animals born before 2006 also with genotypes on the higher density marker panel. The concordance between the actual and imputed genotypes in the test group of animals did not vary across chromosomes and was on average 95%; the concordance between actual and imputed alleles was, on average, 97% across all SNPs. Genomic predictions were undertaken across a range of production and functional traits for the 764 test group animals using either their real or imputed genotypes. Little or no mean difference in the genomic predictions was evident when comparing direct genomic values (DGVs) using real or imputed genotypes. The average correlation between the DGVs estimated using the real or imputed genotypes for the 15 traits included in the Irish total merit index was 0.97 (range of 0.92 to 0.99), indicating good concordance between proofs from real or imputed genotypes. Results show that a commercially available high-density marker panel can be imputed from a commercially available lower density marker panel, which will also have a lower cost, thereby facilitating a reduction in the cost of genomic selection. Increased available numbers of genotyped and phenotyped animals also has implications for increasing the accuracy of genomic prediction in the entire population and thus genetic gain using genomic selection.

Short communication: genetic relationships between the Holstein cow populations of three European dairy countries.

The degree of relatedness was studied in 3 dairy cow populations from Great Britain (GBR), Italy (ITA), and Ireland (IRL) by using cows born from 2003 to 2006. Effective population size, inbreeding coefficient (F), and average relationship in the top and bottom 4,000 cows ranked on a profit index value (PIV) or milk yield evaluations were studied. Average inbreeding was approximately 2% in GBR and ITA, was 1% in IRL, but was slightly more than 2% when the joint pedigree was used. The average F for the joint population was 10 to 15% higher than estimates averaged across the 3 populations, reflecting the increased completeness of pedigree information in the joint pedigree. Effective population size in the joint pedigree was approximately 12% lower than estimates within the individual countries. The average genetic relationships for the top 4,000 PIV cows were not markedly different from those based on milk evaluation in GBR and ITA, but were approximately 2% lower in IRL. This was due to the use of an index with less weight on production traits in IRL compared with GBR and ITA. However, selection of the top 4,000 cows on PIV reduced the degree of relatedness across the 3 countries. The use of common sires accounted for most of the relatedness across the 3 countries, more than did the use of related sires or common foreign dams.

Consequences of selection for improving production traits on the frequency of deleterious alleles for fitness.

In this study the effect of artificial selection on BLUP EBV for production traits on the allele frequencies of a pleiotropic QTL affecting both production and disease susceptibility was investigated. Stochastic simulations were used to model artificial selection on a production trait that is controlled, in part, by a biallelic QTL that also controls susceptibility to disease. The QTL allele increasing production also increased susceptibility to disease. Different modes of action and proportions of variation accounted for by the QTL were assessed for the production trait. The main results indicated that alleles that confer susceptibility to the disease could be maintained in the population over a long period, depending on the mode of action of the QTL. In addition, the results of the study indicate that, under various conditions, it is possible to find pleiotropic QTL that control 2 traits despite these traits appearing to be uncorrelated. Therefore, in practice, an estimate of the genetic correlation between 2 traits may be misleading when the presence of such a QTL exists. The results of this study have implications for breeding programs. For example, if a pleiotropic QTL exists that favors heterozygotes for a production trait, it would be very difficult to remove disease susceptibility alleles via traditional selection methods.

Inbreeding effects on postweaning production traits, conformation, and calving performance in Irish beef cattle.

The objective of this study was to quantify the effect of inbreeding on carcass quality, growth rate, live conformation measures, and calving performance in purebred populations of Charolais, Limousin, Simmental, Hereford, and Angus beef cattle using data from Irish commercial and pedigree herds. Variables analyzed are reflective of commercial farming practices. Inbreeding was included in a linear mixed model as either a class variable or a linear continuous variable. Nonlinear effects were nonsignificant across all traits. Inbred animals had decreased carcass weight and less carcass fat. The effects of inbreeding were more pronounced in the British beef breeds. Effects for carcass weight ranged from -0.87 kg (Charolais) to -1.90 kg (Hereford) per 1% increase in inbreeding. Inbred Charolais and Hereford animals were younger at slaughter by 3 and 5 d, respectively, per percentage of increase in inbreeding, whereas the effect of inbreeding on age at slaughter differed significantly with animal sex in the Limousin and Angus breeds. Inbred Limousin and Angus heifers were younger at slaughter by 5 and 7 d, respectively, per percentage of increase in inbreeding. Continental animals were more affected by inbreeding for live muscling and skeletal conformational measurements than the British breeds; inbred animals were smaller and narrower with poorer developed muscle. Calf inbreeding significantly affected perinatal mortality in Charolais, Simmental, and Hereford animals. The effects were dependent upon dam parity and calf sex; however, where significant, the association was always unfavorable. Dam inbreeding significantly affected perinatal mortality in Limousin and Hereford animals. Effects differed by parity in Limousins. Inbred first-parity Angus dams had a greater incidence of dystocia. Although the effects of inbreeding were some-times significant, they were small and are unlikely to make a large financial effect on commercial beef production in Ireland.

Inbreeding effects on milk production, calving performance, fertility, and conformation in Irish Holstein-Friesians.

The objective of this study was to determine the effect of inbreeding on milk production, somatic cell count, fertility, survival, calving performance, and cow conformation in Irish Holstein-Friesian pluriparous dairy cows. Inbreeding was included in a linear mixed model as either a class variable or a continuous variable, where higher order polynomials of the latter were also tested in the model as an indicator of nonlinear inbreeding depression. The effects of dam inbreeding and calf inbreeding on calving-related traits were analyzed separately. Inbreeding had a deleterious effect on most of the traits analyzed, although inbreeding depression was sometimes nonlinear or differed significantly across parities. A primiparous animal, 12.5% inbred (i.e., following the mating of noninbred half-sibs), had milk, fat, and protein yields reduced by 61.8, 5.3, and 1.2 kg, respectively; fat and protein concentrations reduced by 0.05 and 0.01%, respectively; and somatic cell scores (i.e., natural log of somatic cell count divided by 1,000) increased by 0.03. The 12.5% inbred animal was also expected to have a 2% greater incidence of dystocia, a 1% greater incidence of stillbirth, a 0.7% greater incidence of male calves, an increase in calving interval of 8.8 d, an increase in age at first calving of 2.5 d, and a reduced survival to second lactation of 4 percentage units. Inbred animals were also taller, narrower, and more angular. Although the effects of inbreeding were statistically significant, they were small and are unlikely to cause great financial loss on Irish dairy farms.

Inbreeding trends and pedigree analysis of Irish dairy and beef cattle populations.

The objective of this study was to determine the inbreeding levels and to analyze the pedigree of Irish purebred populations of Charolais, Limousin, Hereford, Angus, and Simmental beef cattle, as well as the Holstein-Friesian dairy breed. Pedigree analyses included quantifying the depth of known pedigree, average generation intervals, effective population size, the effective number of founders, ancestors, and founder genomes, as well as identifying the most influential animals within the current population of each breed. The annual rate of increase in inbreeding over the past decade was 0.13% (P < 0.001) in the Hereford, 0.06% (P < 0.001) in the Simmental, and 0.10% (P < 0.001) in the Holstein-Friesian breeds. Inbreeding in the other breeds remained relatively constant over the past decade. Herefords had the greatest mean inbreeding in 2004, at 2.19%, whereas Charolais had the lowest, at 0.54%. Over half of each purebred population in 2004 was inbred to some degree; the population with the greatest proportion of animals inbred was the Hereford breed (85%). All 6 breeds displayed a generation interval of approximately 6 yr in recent years. In the pure-bred females born in 2004, the 3 most influential animals contributed between 11% (Limousin) and 24% (Hereford) of the genes. Effective population size was estimated for the Hereford, Simmental, and Holstein-Friesian only, and was 64, 127, and 75, respectively. The effective number of founders varied from 55 (Simmental) to 357 (Charolais), whereas the effective number of ancestors varied from 35 (Simmental and Hereford) to 82 (Limousin). Thus, despite the majority of animals being inbred, the inbreeding level across breeds is low but rising at a slow rate in the Hereford, Simmental, and Holstein-Friesian.

Cumulative discounted expressions of sire genotypes for the complex vertebral malformation and beta-casein loci in commercial dairy herds.

Based on discounted gene-flow principles, a set of recursive equations was developed to quantify the value of using sires with a specific genotype for an identified gene in a commercial dairy herd. Two examples were used to demonstrate the usefulness of the method. The first example deals with the implications of using sires that are known carriers of the lethal recessive genetic defect, complex vertebral malformation (CVM). The second example examines the value of using sires homozygous for the A2 allele of beta-casein. Results are presented in terms of cumulative discounted expressions. These are then multiplied by the economic values of specific genotypes to determine the cost or benefit of using these sires. In general, the degree of mortality and the required price reduction for carrier sires increased as the proportion of carrier sires used, the duration of sire use, and the initial frequency in the cow herd increased. A semen discount of 3.10 pound sterling per CVM straw used would be required to offset the expected mortality when 20% of CVM carrier sires are used for 3 yr when 5% of cows are carriers. The cumulative discounted expressions' of using sires homozygous for the A2 allele of beta-casein also increased when the proportion and duration of carrier sire use and the initial frequency of the A2 allele increased. Assuming an A2A2 cow is worth 160 pound sterling more than a non-A2A2 cow, the expected benefit of using A2A2 sires in a 100-cow herd for 5 yr would be 57 pound sterling,120 for a 20-yr planning horizon. The results of this study demonstrate how the starting gene frequency in the herd, and the proportion and duration of use of sires of particular genotypes are critical to the economic implications of using single genes in commercial dairy farms.

Impact of nonadditive genetic effects in the estimation of breeding values for fertility and correlated traits.

The effects of inbreeding, heterosis, recombination loss, and percentage Holstein on the estimation of predicted transmitting abilities for fertility traits (calving interval, number of days from calving to first insemination, nonreturn rate, number of inseminations) and correlated traits (milk yield at test nearest d 110 and body condition score) were examined in a mixed population of Holstein and Friesian cattle. An unfavorable effect of percentage Holstein on calving interval was observed, resulting in a 12-d increase for pure Holsteins compared with pure Friesians. Insemination traits were less affected by percentage Holstein, with 3% more animals returning to first service within 56 d and 0.1 more inseminations required for Holstein animals. Heterosis and recombination loss affected some of the traits. Heterosis had a favorable effect on yield, with a 0.35-kg difference between a pure and cross-bred animal for test milk. There was a reduction of 1 d to first insemination between a pure and first-crossbred animal. Inbreeding had a significant and unfavorable effect on all traits. The difference between a noninbred animal and an animal with an inbreeding coefficient of 10% was a 2.8-d increase in calving interval, a 1.7-d increase in days to first insemination, a 1% increased probability to return to estrus at first service, 0.03 more inseminations, a 0.27-unit decrease in body condition, and a 0.54-kg decrease in milk on test nearest d 110. The effect of inbreeding depression was more pronounced at higher levels of inbreeding. The rank correlations between the predicted transmitting abilities for fertility and correlated traits, with and without the additional nonadditive effects in the model, were over 0.99. Steps should be taken to control the rise in inbreeding, or the effects on fertility and correlated traits such as milk production will begin to manifest themselves.

Inbreeding trends and application of optimized selection in the UK Holstein population.

Important increases in the rates of inbreeding have recently been observed in dairy cattle populations, and methods have been proposed to address these increases. The aims of this study were to estimate the current level and rates of inbreeding in the UK Holstein population and to investigate the potential of applying optimized selection to manage the rates of inbreeding. Inbreeding coefficients were calculated for the entire UK Holstein population using 1940 as the base year. Rates of inbreeding were obtained for 3 time periods by regressing mean inbreeding coefficients on the year of birth of the animals. The expected average pedigree index and expected inbreeding of offspring using optimized contributions for a given set of selection candidates was compared to the expected pedigree index and inbreeding of offspring for the same set of selection candidates using observed contributions. The rate of inbreeding in the UK Holstein population has increased substantially since 1990 when compared to previous time periods. This increase is most likely due to the large influence of a few related sires on the breed in the mid- to late 1980s. The introduction of the individual animal model in the early 1990s may also have contributed to increased inbreeding. Optimized selection appears to represent a promising selection tool, not only to manage rates of inbreeding, but also to increase genetic gain at the same rate of inbreeding.

Genotype x environment interaction for grazing versus confinement. I. Production traits.

The objective of this study was to investigate the possible existence of a genotype x environment interaction (GxE) for production traits of US Holsteins in grazing versus confinement herds. Grazing herds were defined as those that utilized grazing for at least 6 mo and were enrolled in dairy herd improvement (DHI). Control herds were confinement DHI herds of comparable size in similar regions. The performance of daughters in grazing herds and control herds was examined using linear regression of mature equivalent milk, fat, and protein yield on the November 2000 USDA-DHI predicted transmitting abilities (PTA) of their sires for those traits. Heritabilities and genetic correlations were estimated using restricted maximum likelihood in a bivariate animal model that considered the same trait in different environments as different traits. Product-moment and rank correlations were calculated between sires' estimated breeding values, estimated separately in both environments. For grazing herds, the coefficient of regression of milk, fat and protein on PTA were 0.78, 0.76, and 0.78, respectively. Corresponding coefficients in the control herds were 0.99, 0.96, and 0.98. Estimates of heritability for the traits ranged from 0.2 to 0.25, and differences between grazing and control environments were small. Estimates of the genetic correlations for the traits in both environments were 0.89, 0.88, and 0.91 for milk, fat, and protein, respectively. Within-quartile analyses revealed a lower correlation for milk and protein between the upper and lower grazing quartiles, while the same quartiles for the control herds did not differ from unity. Rank correlation coefficients between sire estimated breeding values from the 2 environments were 0.59, 0.63, and 0.66 for milk, fat, and protein, respectively. The mean rank change for the top 100 sires between the two environments was 27. The regression coefficients indicate that expected daughter differences may be overstated by current sire PTA in grazing herds. Genetic correlations less than unity suggests that there is, at least, some reranking among sires in both environments, while the rank correlations indicate the possibility of sire reranking when evaluations were performed within management system. However, differences are not so large as to justify separate genetic evaluations for each system.

Genotype x environment interaction for grazing vs. confinement. II. Health and reproduction traits.

Continual selection for increased milk yield for more than 40 yr, combined with the antagonistic relationship between increasing yield, somatic cell count, and fertility, have resulted in sires that may not be optimal for producing daughters for grazing systems where seasonal calving is very important. The objective of this study was to investigate the possible existence of a genotype x environment interaction (G x E) in grazing vs. confinement herds within the United States for lactation average somatic cell score (LSCS), days open (DO), days to first service (DFS), and number of services per conception (SPC). Grazing herds were defined as those that utilized grazing for at least 6 mo each year and were enrolled in Dairy Herd Improvement (DHI). Control herds were confinement DHI herds of similar size in the same states. For LSCS, the performance of daughters in grazing and control herds was examined using linear regression of LSCS on the November 2000 USDA-DHIA sire predicted transmitting abilities (PTA) for SCS. Genetic parameters for all traits were estimated using REML in a bivariate animal model that treated the same trait in different environments as different traits. Rank correlations were calculated between sires' estimated breeding values for LSCS, calculated separately for sires in both environments. The coefficient of regression of daughter LSCS on sire PTA was less in grazing herds than in control herds. The coefficient of regression for control herds was closer to expectation. Estimates of heritability were approximately 0.12 for LSCS, and less than 0.05 for the reproduction traits. Heritabilities for DO, DFS, and SPC were slightly higher for control herds. Estimates of genetic correlation for each reproductive trait between the 2 environments were high and not significantly different from unity. Generally, these traits appear to be under similar genetic control, but a lower coefficient of regression of LSCS on sire PTA for SCS in grazing herds suggests differences in daughter performance in grazing herds may be overstated based on current PTA for SCS.

Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens.

The rate of pathogen elimination determines the extent and consequences of an infection. In this context, the spleen with its highly specialized lymphoid compartments plays a central role in clearing blood-borne pathogens. Splenic marginal zone B cells (MZ), by virtue of their preactivated state and topographical location, join B1 B cells to generate a massive wave of IgM producing plasmablasts in the initial 3 days of a primary response to particulate bacterial antigens. Because of the intensity and rapidity of this response, combined with the types of antibodies produced, splenic MZ and B1 B cells endowed with a "natural memory" provide a bridge between the very early innate and the later appearing adaptive immune response.

Ku80 is required for addition of N nucleotides to V(D)J recombination junctions by terminal deoxynucleotidyl transferase.

V(D)J recombination generates a remarkably diverse repertoire of antigen receptors through the rearrangement of germline DNA. Terminal deoxynucleotidyl transferase (TdT), a polymerase that adds random nucleotides (N regions) to recombination junctions, is a key enzyme contributing to this diversity. The current model is that TdT adds N regions during V(D)J recombination by random collision with the DNA ends, without a dependence on other cellular factors. We previously demonstrated, however, that V(D)J junctions from Ku80-deficient mice unexpectedly lack N regions, although the mechanism responsible for this effect remains undefined in the mouse system. One possibility is that junctions are formed in these mice during a stage in development when TdT is not expressed. Alternatively, Ku80 may be required for the expression, nuclear localization or enzymatic activity of TdT. Here we show that V(D)J junctions isolated from Ku80-deficient fibroblasts are devoid of N regions, as were junctions in Ku80-deficient mice. In these cells TdT protein is abundant at the time of recombination, localizes properly to the nucleus and is enzymatically active. Based on these data, we propose that TdT does not add to recombination junctions through random collision but is actively recruited to the V(D)J recombinase complex by Ku80.

B1 cells: similarities and differences with other B cell subsets.

Since their discovery, B1 B cells' origins and developmental pathways have eluded characterization. In the past year, focus on B1 B cells has shifted dramatically from developmental to functional aspects of these cells. Most advances have been made in describing the physiological activities of B1 cells, including their migration, activation by antigen and role in both autoimmunity and malignancy.