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Waldmann P.,University of Natural Resources and Life Sciences, Vienna | Waldmann P.,Linköping University | Meszaros G.,University of Natural Resources and Life Sciences, Vienna | Gredler B.,Qualitas AG | And 2 more authors.
Frontiers in Genetics | Year: 2013

The number of publications performing genome-wide association studies (GWAS) has increased dramatically. Penalized regression approaches have been developed to overcome the challenges caused by the high dimensional data, but these methods are relatively new in the GWAS field. In this study we have compared the statistical performance of two methods (the least absolute shrinkage and selection operator-lasso and the elastic net) on two simulated data sets and one real data set from a 50 K genome-wide single nucleotide polymorphism (SNP) panel of 5570 Fleckvieh bulls. The first simulated data set displays moderate to high linkage disequilibrium between SNPs, whereas the second simulated data set from the QTLMAS 2010 workshop is biologically more complex. We used cross-validation to find the optimal value of regularization parameter γ with both minimum MSE and minimum MSE + 1SE of minimum MSE. The optimal γ values were used for variable selection. Based on the first simulated data, we found that the minMSE in general picked up too many SNPs. At minMSE + 1SE, the lasso didn't acquire any false positives, but selected too few correct SNPs. The elastic net provided the best compromise between few false positives and many correct selections when the penalty weight a was around 0.1. However, in our simulation setting, this a value didn't result in the lowest minMSE + 1SE. The number of selected SNPs from the QTLMAS 2010 data was after correction for population structure 82 and 161 for the lasso and the elastic net, respectively. In the Fleckvieh data set after population structure correction lasso and the elastic net identified from 1291 to 1966 important SNPs for milk fat content, with major peaks on chromosomes 5, 14, 15, and 20. Hence, we can conclude that it is important to analyze GWAS data with both the lasso and the elastic net and an alternative tuning criterion to minimum MSE is needed for variable selection. © 2013 Waldmann, Mészáros, Gredler, Fuerst and Sölkner.


Pausch H.,TU Munich | Kolle S.,Ludwig Maximilians University of Munich | Kolle S.,University College Dublin | Wurmser C.,TU Munich | And 7 more authors.
PLoS Genetics | Year: 2014

Genetic variants underlying reduced male reproductive performance have been identified in humans and model organisms, most of them compromising semen quality. Occasionally, male fertility is severely compromised although semen analysis remains without any apparent pathological findings (i.e., idiopathic subfertility). Artificial insemination (AI) in most cattle populations requires close examination of all ejaculates before insemination. Although anomalous ejaculates are rejected, insemination success varies considerably among AI bulls. In an attempt to identify genetic causes of such variation, we undertook a genome-wide association study (GWAS). Imputed genotypes of 652,856 SNPs were available for 7962 AI bulls of the Fleckvieh (FV) population. Male reproductive ability (MRA) was assessed based on 15.3 million artificial inseminations. The GWAS uncovered a strong association signal on bovine chromosome 19 (P = 4.08×10-59). Subsequent autozygosity mapping revealed a common 1386 kb segment of extended homozygosity in 40 bulls with exceptionally poor reproductive performance. Only 1.7% of 35,671 inseminations with semen samples of those bulls were successful. None of the bulls with normal reproductive performance was homozygous, indicating recessive inheritance. Exploiting whole-genome re-sequencing data of 43 animals revealed a candidate causal nonsense mutation (rs378652941, c.483C>A, p.Cys161X) in the transmembrane protein 95 encoding gene TMEM95 which was subsequently validated in 1990 AI bulls. Immunohistochemical investigations evidenced that TMEM95 is located at the surface of spermatozoa of fertile animals whereas it is absent in spermatozoa of subfertile animals. These findings imply that integrity of TMEM95 is required for an undisturbed fertilisation. Our results demonstrate that deficiency of TMEM95 severely compromises male reproductive performance in cattle and reveal for the first time a phenotypic effect associated with genomic variation in TMEM95. © 2014 Pausch et al.


Fuerst-Waltl B.,University of Natural Resources and Life Sciences, Vienna | Fuerst C.,ZuchtData EDV Dienstleistungen GmbH
Livestock Science | Year: 2010

Most countries worldwide already include functional traits in the breeding goals for cattle. Among those are e.g. reproductive traits or longevity while traits regarding calves or heifers are hardly considered. Mortality, but also culling of heifers before first calving may result in higher replacement costs but also in reduced possibility for selection and is thus of importance in cattle breeding. Thus, the aim of this investigation was to explore the genetic background of postnatal mortality and involuntary culling in Austrian Fleckvieh (dual purpose Simmental) calves and replacement heifers. The following periods were defined for analyses: P1 = 48. h to 30. days, P2 = 31 to 180. days, P3 = 181 to 365. days, P4 = 366. days to first calving or a maximum age of 1200. days if no calving was reported, P5 = birth to age at first calving or a maximum age of 1200. days if no calving was reported, P4S = heifers having at least one insemination slaughtered in P4, defined as involuntarily culled. After data editing records of more than 86,000 calves and heifers were investigated. Mortality rates were 1.85, 1.39, 0.36, 0.70, and 5.61% for the defined periods P1-P5, respectively; 7.78% of heifers were involuntarily culled (P4S). For the estimation of genetic parameters a linear and threshold sire model and a linear animal model with the random effects herd * year and sire as well as the fixed effects year * month, number of dam's parity, and calving ease were applied. In total, the pedigree consisted of 11,609 animals (sire model, sire-dam relationship) and 237,113 animals (animal model). For mortality traits, heritabilities ranged from < 0.0001 (P3) to 0.018 (P5) for the linear models, and 0.001 (P3) to 0.072 (P1) for the threshold model, respectively. Heritabilities for involuntary culling (P4S) were 0.024, 0.021 and 0.067 for the linear animal, linear sire and threshold sire model, respectively. The rank correlations were > 0.99 between random effects of sires obtained with linear sire and threshold sire models and were lower (r= 0.77 to 0.90) for animal and sire models, respectively. Total calf and heifer mortality is higher than stillbirth. Consequently, its economic impact on cattle breeding should not be neglected. Based on the results obtained in this study selection against higher postnatal mortality and involuntary culling of heifers should be possible. Furthermore, monitoring of the population and of extreme bulls might be very useful for breeding organisations to avoid deterioration in these traits. © 2010 Elsevier B.V.


Egger-Danner C.,ZuchtData EDV Dienstleistungen GmbH | Willam A.,University of Natural Resources and Life Sciences, Vienna | Fuerst C.,ZuchtData EDV Dienstleistungen GmbH | Schwarzenbacher H.,ZuchtData EDV Dienstleistungen GmbH | Fuerst-Waltl B.,University of Natural Resources and Life Sciences, Vienna
Journal of Dairy Science | Year: 2012

A complex deterministic approach was used to model the breeding goal and breeding structure for the Austrian Fleckvieh (dual-purpose Simmental) breed. The reference breeding goal corresponded to the current total merit index (TMI-R), where dairy traits have a relative weight of 37.9% and fitness traits of 43.7% (beef traits 16.5%; milkability 2%). The breeding program was characterized by 280,000 cows under performance recording, 3,200 bull dams, 100 test bulls with a test capacity of 25%, and 15 proven bulls and 8 bull sires per year. The annual monetary genetic gain (AMGG) was generated mainly by increases in milk fat and milk protein yield (80.6%) and only to a small extent by fitness traits (6.6%). The inclusion of direct health traits (early reproductive disorders, cystic ovaries, and mastitis) with their economic weights increased the relative AMGG for fitness traits from 6.6 to 11.2%. The presently slightly negative AMGG for fertility index and udder health changed in a positive direction. Increasing the weight on the direct health traits by 50% resulted in a further shift toward fitness and health. The effect of strategies using genomic information in a total merit index (TMI) with varying weights on fitness and health traits was also analyzed. The conventional progeny-testing scheme was defined as the reference breeding program. A breeding program was considered to be genomically enhanced (GS50) when 50% of inseminations of herdbook cows and of bull dams were from young bulls with a genomic TMI, and a second program (GS100) did not rely on progeny-tested bulls at all. For GS50, a clear shift of the relative gain in AMGG toward fitness and health traits was observed for all 3 TMI scenarios, as a result of larger progeny groups and a shorter generation interval. For GS100, where no gene flow from progeny-tested bulls was assumed, the genetic gain per generation was lower for the fertility and udder health index but higher per year. The results based on natural genetic gain per year showed that no positive genetic response for fertility and udder health index were achieved for TMI-R (without the inclusion of direct health traits) in GS50 and GS100. The direction of the genetic trend was determined by the weights given to fertility and udder health indices within the TMI. When appropriate weights generated a clear positive trend, GS50 and GS100 reinforced this trend. © 2012 American Dairy Science Association.


Koeck A.,University of Natural Resources and Life Sciences, Vienna | Heringstad B.,Norwegian University of Life Sciences | Egger-Danner C.,ZuchtData EDV Dienstleistungen GmbH | Fuerst C.,ZuchtData EDV Dienstleistungen GmbH | Fuerst-Waltl B.,University of Natural Resources and Life Sciences, Vienna
Journal of Dairy Science | Year: 2010

The performance of different models for genetic analyses of clinical mastitis in Austrian Fleckvieh dual-purpose cows was evaluated. The main objective was to compare threshold sire models (probit and logit) with linear sire and linear animal models using REML algorithm. For comparison, data were also analyzed using a Bayesian threshold sire model. The models were evaluated with respect to ranking of sires and their predictive ability in cross-validation. Only minor differences were observed in estimated variance components and heritability from Bayesian and REML probit models. Heritabilities for probit and logit models were 0.06 and 0.08, respectively, whereas heritabilities for linear sire and linear animal models were lower (0.02). Correlations among ranking of sires from threshold and linear sire models were high (>0.99), whereas correlations between any sire model (threshold or linear) and the linear animal model were slightly lower (0.96). The worst sires were ranked very similar across all models, whereas for the best sires some reranking occurred. Further, models were evaluated based on their ability to predict future data, which is one of the main concerns of animal breeders. The predictive ability of each model was determined by using 2 criteria: mean squared error and Pearson correlation between predicted and observed value. Overall, the 5 models did not differ in predictive ability. In contrast to expectations, sire models had the same predictive ability as animal models. Linear models were found to be robust toward departures from normality and performed equally well as threshold models. © 2010 American Dairy Science Association.


Egger-Danner C.,ZuchtData EDV Dienstleistungen GmbH | Schwarzenbacher H.,ZuchtData EDV Dienstleistungen GmbH | Willam A.,University of Natural Resources and Life Sciences, Vienna
Journal of Dairy Science | Year: 2014

The aim of this study was to quantify the impact of genotyping cows with reliable phenotypes for direct health traits on annual monetary genetic gain (AMGG) and discounted profit. The calculations were based on a deterministic approach using ZPLAN software (University of Hohenheim, Stuttgart, Germany). It was assumed that increases in reliability of the total merit index (TMI) of 5, 15, and 25 percentage points were achieved through genotyping 5,000, 25,000, and 50,000 cows, respectively. Costs for phenotyping, genotyping, and genomic estimated breeding values vary between €150 and €20 per cow. The gain in genotyping cows for traits with medium to high heritability is more than for direct health traits with low heritability. The AMGG is increased by 1.5% if the reliability of TMI is 5 percentage points higher (i.e., 5,000 cows genotyped) and 6.53% higher AMGG can be expected when the reliability of TMI is increased by 25 percentage points (i.e., 50,000 cows genotyped). The discounted profit depends not only on the costs of genotyping but also on the population size. This study indicates that genotyping cows with reliable phenotypes is feasible to speed up the availability of genomic estimated breeding values for direct health traits. But, because of the huge amount of valid phenotypes and genotypes needed to establish an efficient genomic evaluation, it is likely that financial constraints will be the main limiting factor for implementation into breeding program such as Fleckvieh Austria. © 2014 American Dairy Science Association.


Fuerst-Waltl B.,University of Natural Resources and Life Sciences, Vienna | Fuerst C.,ZuchtData EDV Dienstleistungen GmbH
Journal of Dairy Science | Year: 2012

The aim of this study was to estimate inbreeding depression for juvenile mortality in Austrian Brown Swiss replacement heifers born in the years 2001 to 2007. After data editing, records of 69,571 animals were investigated. In total, the pedigree consisted of 203,894 animals. Mean and median inbreeding coefficients were 0.0514 and 0.0475, respectively. The following periods were defined for analyses of juvenile mortality: P1 = 48. h to 30 d, P2 = 31 to 180 d, P3 = 181 to the day before first calving or a maximum age of 1,200. d if no calving was reported, P4 = 48. h to the day before age at first calving or a maximum age of 1,200. d if no calving was reported. Mortality during the first 30. d of life was 3.2%; in the total rearing period, 9.3% of the heifers died (excluding slaughtered and exported animals). For the estimation of the effect of inbreeding and of genetic parameters a linear animal model with the random effects herd-year of birth and animal as well as the fixed effects year of birth-month of birth and dam parity, and the continuous effect of inbreeding coefficient (linear and quadratic) was applied. The model was reduced to the linear effect of inbreeding as the quadratic term was not found to have a significant effect. Inbreeding significantly affected all traits unfavorably. In the full rearing period (P4), heifer calves with an inbreeding coefficient of 0.10 had a 4.9% higher mortality rate than heifer calves with no inbreeding. © 2012 American Dairy Science Association.


Koeck A.,University of Natural Resources and Life Sciences, Vienna | Heringstad B.,Norwegian University of Life Sciences | Egger-Danner C.,ZuchtData EDV Dienstleistungen GmbH | Fuerst C.,ZuchtData EDV Dienstleistungen GmbH | And 2 more authors.
Journal of Dairy Science | Year: 2010

The objectives of this study were to investigate genetic associations between clinical mastitis (CM) and different somatic cell count traits, and to examine their relationships, in terms of estimated breeding values, with other traits that are routinely evaluated in Austrian Fleckvieh dual-purpose cows. Records on veterinary treatments of CM were available from the Austrian health-monitoring project. For CM, 3 intervals in early lactation were considered: -10 to 50 d, 51 to 150 d, and -10 to 150 d after calving. Within each interval, absence or presence of CM was scored as 1 or 0 based on whether or not the cow had recorded at least one veterinary treatment of CM. The average somatic cell score of the first 2 test-days after calving was defined as early lactation average somatic cell score, and lactation mean somatic cell score was the average of all test-day somatic cell scores from 8 to 305 d after calving. Subclinical mastitis was expressed as a binary trait based on prolonged elevated somatic cell counts. If somatic cell counts on 3 consecutive test-days in the interval from 8 to 305 d after calving were above 200,000 cells/mL, the binary variable subclinical mastitis was defined as 1 and otherwise 0. Records of Austrian Fleckvieh cows, with calving from January 1, 2007, to February 28, 2009, were analyzed using univariate and bivariate sire models. Threshold liability models were applied for binary traits, and Gaussian models were used for early lactation average somatic cell score and lactation mean somatic cell score. A Bayesian approach using Gibbs sampling was applied for genetic analyses. Posterior means of heritability of liability to CM were 0.06 and 0.02 in the first and second interval, respectively, and 0.05 in the full period (-10 to 150 d). Heritability estimates of somatic cell count traits were higher (0.09 to 0.13). The posterior mean of the genetic correlation between CM in lactation period 1 (-10 to 50 d after calving) and 2 (51 to 150 d after calving) was close to unity. Posterior means of genetic correlations between CM and somatic cell count traits ranged from 0.64 to 0.77. Because CM and somatic cell count describe different aspects of udder health, information on both traits should be considered for selection of bulls. Correlations of sire breeding values revealed that especially the udder conformation trait udder depth may be useful as additional information to reduce both CM and somatic cell count. © 2010 American Dairy Science Association.


Koeck A.,University of Natural Resources and Life Sciences, Vienna | Egger-Danner C.,ZuchtData EDV Dienstleistungen GmbH | Fuerst C.,ZuchtData EDV Dienstleistungen GmbH | Obritzhauser W.,Chamber of Veterinaries | Fuerst-Waltl B.,University of Natural Resources and Life Sciences, Vienna
Journal of Dairy Science | Year: 2010

The objective of this study was to estimate genetic parameters for various reproductive disorders based on veterinary diagnoses for Austrian Fleckvieh (Simmental) dual-purpose cattle. The health traits analyzed included retained placenta, puerperal diseases, metritis, silent heat and anestrus, and cystic ovaries. Three composite traits were also evaluated: early reproductive disorders, late reproductive disorders, and all reproductive disorders. Heritabilities were estimated with logit threshold sire, linear sire, and linear animal models. The threshold model estimates for heritability ranged from 0.01 to 0.14, whereas the linear model estimates were lower, ranging from 0.005 to 0.04. Rank correlations among random effects of sires from linear and threshold sire models were high (>0.99), whereas correlations between any sire model (linear, threshold) and the linear animal model were lower (0.88-0.92). Genetic correlations among reproductive disorders, fertility traits, and milk yield were estimated with bivariate linear animal models. Fertility traits included interval from calving to first insemination, nonreturn rate at 56 d, and interval between first and last insemination. Milk yield was calculated as the mean from test-day 1 and test-day 2 after calving. Estimated genetic correlations were 1 among metritis, retained placenta, and puerperal diseases and 0.85 between silent heat-anestrus and cystic ovaries. Low to moderate correlations (-0.01 to 0.68) were obtained among the other disorders. Genetic correlations between reproductive disorders and fertility traits were favorable, whereas antagonistic relationships were observed between milk yield in early lactation and reproductive disorders. Pearson correlations between estimated breeding values for reproductive disorders and other routinely evaluated traits were computed, which revealed noticeable favorable relationships to longevity, calving ease maternal, and stillbirth maternal. The results showed that data from the Austrian health monitoring project can be used for genetic selection against reproductive disorders in Fleckvieh cattle. © 2010 American Dairy Science Association.


Jung S.,TU Munich | Pausch H.,TU Munich | Langenmayer M.C.,Ludwig Maximilians University of Munich | Schwarzenbacher H.,ZuchtData EDV Dienstleistungen GmbH | And 3 more authors.
BMC Genomics | Year: 2014

Background: Bovine hereditary zinc deficiency (BHZD) is an autosomal recessive disorder of cattle, first described in Holstein-Friesian animals. Affected calves suffer from severe skin lesions and show a poor general health status. Recently, eight calves with the phenotypic appearance of BHZD have been reported in the Fleckvieh cattle population.Results: In spite of the similar disease phenotypes, SLC39A4, the gene responsible for BHZD in Holstein-Friesian was excluded as underlying gene for the disorder in the affected Fleckvieh calves. In order to identify the disease-associated region, genotypes of eight affected calves obtained with the Illumina BovineHD BeadChip comprising 777,962 SNPs were contrasted with the genotypes of 1,339 unaffected animals. A strong association signal was observed on chromosome 21 (P = 5.87 × 10-89). Autozygosity mapping in the eight affected animals revealed a common segment of extended homozygosity encompassing 1,023 kb (BTA 21: 70,550,045 - 71,573,501). This region contains 17 genes/transcripts, among them two genes encoding gastro-intestinal zinc transporters (CRIP1, CRIP2). However, no mutation that was compatible with recessive inheritance could be detected in these candidate genes. One of the affected calves was re-sequenced together with 42 unaffected Fleckvieh animals. Analysis of the sequencing data revealed a nonsense mutation (p.W215X) in a phospholipase encoding gene (PLD4) as candidate causal polymorphism. To confirm the causality, genotypes of the p.W215X-mutation were obtained from 3,650 animals representing three different breeds. None of the unaffected animals was homozygous for the defect allele, while all eight affected calves were homozygous. The deleterious effect of the mutation is manifested in a significantly lower survival rate of descendants from risk matings when compared with the survival rate of descendants from non-risk matings. The deleterious allele has an estimated frequency of 1.1% in the Fleckvieh population.Conclusion: Our results provide strong evidence that a newly identified recessive disorder in the Fleckvieh population is caused by a nonsense mutation in PLD4, most likely resulting in an impaired function of the encoded protein. Although the phenotype of affected calves strongly resembles BHZD, a zinc deficiency resulting from malabsorption is unlikely to be responsible for the diseased Fleckvieh calves. © 2014 Jung et al.

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