B. Bapst1, M. Bohlouli2, S. König2 and K. Brügemann2
1Qualitas AG, Zug, Switzerland; 2University of Giessen, Department of Animal Breeding and Pet Genetics, Giessen, Germany Email: Beat.Bapst@qualitasag.ch
Introduction In the context of discussions on climate change the question arises whether dairy cows respond differently to changing weather conditions and therefore whether genotype x environment interactions (GxE) exist. Udder health (UH) is one of the mos t important functional traits in dairy cattle. UH is not only important from the point of view of quality requirements but also for economic reasons (Hogeveen et al., 2011) as well as animal welfare reasons. Somatic cell count (SCC) or somatic cell score (SCS) have been included in breeding strategies as auxiliary traits for UH because the genetic correlation between SCS and mastitis incidence is up to 0.67 (Coffey et al., 1986). The investigations presented here have been initiated with Swiss Holstein (HO) and Swiss Simmental (SI) by considering countrywide weather data in order to investigate the impact of the breeding strategy on the response to environmental changes. HO represents dairy breeds and SI is a classical dual purpose breed and our hypothesis was that dairy breeds react much more sensitive than dual purpose breeds on changing environmental conditions.
Materials and Methods We developed a reaction norm model, where we included weather data in a random regression test day model (RRTDM), which was derived from the official Swiss genetic evaluation system. The applied RRTDM was built based on previous work from Bohmanova et al. (2008). The trait of interest was SCS. Daily temperature-humidity indexes (THI, NRC (1971)) from 60 official federal weather stations were assigned to each HO and SI herd from swissherdbook (www.swissherdbook.ch) as a continuous environmental descriptor over a time period of 10 years. After data editing, 1,106,410 and 7,340,498 test day (TD) records remained from 61,064 SI and from 363,472 HO cows, respectively. For fitting the additive genetic and the permanent environment effects, the RRTDM was extended with the covariates days in milk (DIM) and THI, both with Legendre polynomials of order 3.
Results First results show that the additive genetic variance of SI and HO concerning SCS along the DIM and along the THI axis have not the same course (Figure 1 and 2). Changes in additive genetic variance along either gradient show sensitivity to this particular gradient. Therefore it can be observed that HO is more sensitive to DIM than to THI while SI is more sensitive to THI than to DIM. Further genetic parameters like heritability or genetic correlations differ between the two breeds along THI and along DIM as well. Genetic correlations of SI among specific THI combinations fall several times massively below the threshold of 0.8, which indicates that GxE exist (Robertson, 1959). HO usually stays above 0.8.
Figure 1 Additive genetic (AG) variance of SCS of HO along DIM and THI
Figure 2 Additive genetic (AG) variance of SCS of SI along DIM and THI
Conclusions The preliminary results point out that the dual-purpose breed SI reacts more sensitive to an environmental gradient than the dairy breed HO. This result is unexpected and requires further investigations. Additionally the results indicate that the impact of expanding the model with weather covariates on the breeding value estimation must be evaluated regarding a reranking of sires and dams.
References
Bohmanova, J., F. Miglior, J. Jamrozik, I. Misztal, and P. G. Sullivan. 2008. Comparison of random regression models with Legendre polynomials and linear splines for production traits and somatic cell score of Canadian Holstein cows. J. Dairy Sci. 91:3627–3638.
Coffey, E. M., W. E. Vinson, and R. E. Pearson. 1986. Potential of somatic cell concentration in milk as a sire selection criterion to reduce mastitis in dairy cattle. J.
Dairy Sci. 69:2163–2172.
Hogeveen, H., Huijps, K., and T.J.G.M. Lam. 2011. Economic aspects of mastitis: New developments. New Zealand Veterinary Journal. 59:1, 16-23.
NRC. 1971. A Guide to Environmental Research on Animals. Natl. Acad. Sci., Washington, DC.
Robertson, A. 1959. The sampling variance of the genetic correlation coefficient. Biometrics 15:469–485.
Exploiting massive genomic data to improve fertility and rearing success in Swiss dairy cattle
I. M. Häfliger1, F. R. Seefried2 and C. Drögemüller11Institute of Genetics, University of Bern, Switzerland; 2Qualitas AG, Zug, Switzerland Email: irene.haefliger@vetsuisse.unibe.ch
Since genomic selection had been promoted and firstly introduced in 2008, thousands of cattle had been genotyped for ten thousands of single nucleotide variants (SNV). While genomic selection decreased the generation interval and increased the genetic gain for production traits immensely, many health traits were not yet taken into account. Rather than improving, these important traits worsened in the overall populations.
It is confirmed, that intensive selection for milk production affected fertility and immunity negatively. However, these days genomic breeding values for health traits are implemented and during the last years American Holstein breeders showed, that health and production traits can be improved simultaneously. Nevertheless, through the so-called hitchhiking effect, recessive lethal alleles affecting fertility negatively increased in frequency even though selection pressure was put to improve fertility traits. A reason for the accumulation of recessive embryonic lethal variants is the decreased population size and the thereby increased inbreeding.
Currently, we mine the available genotyping data for certain haplotypes, which impair fertility and rearing success. The general assumption applied is that haplotypes harboring a recessive lethal mutation do not occur in homozygous state within the genotyped normal breeding animals. Thus, we searched for haplotypes in the genome showing a significant depletion from the Hardy-Weinberg equilibrium and successfully identified numerous regions in four Swiss dairy breeds. In order to investigate the effects of such haplotypes, we estimated their impact on reproduction and production traits in a linear mixed model. Furthermore, we performed whole genome sequencing (WGS) of carrier animals to find deleterious variants responsible for embryonic lethality, abortion, stillbirth and other nonviable phenotypes. Up to date, we have more than 400 genomes available and use this data to screen for SNVs and larger structural variants in the genome regions corresponding to the mapped haplotypes.
In addition, we aim to apply the approach of reverse genetics. Thereby, the impact of protein-changing SNVs will be predicted and by genotyping those variants with a customized array, our aim is to demonstrate their effect on certain phenotypes. Through this approach, we intend to early detect reproduction and production diseases affecting calf survival. For example, the APOB-associated cholesterol deficiency in Holstein cattle, for which we have identified the causal mutation and which is phenotypically very unspecific, could have been revealed before thousands of calves had died and an economically significant damage had affected the dairy industry.
Session 08: Impact of animal genetics on animal health and disease
Chromosomal imbalance in a boar causing cleft palate in the offspring and affecting the litter size in sows
A. Grahofer1,2, A. Letko3, I. M. Häfliger3, V. Jagannathan3, A. Ducos4, O. Richard5, V. Peter6, H. Nathues2 and C. Drögemüller31Animal Physiology, Institute of Agricultural Sciences, ETH Zurich, Switzerland; 2Clinic for Swine, Vetsuisse Faculty, University of Bern, Switzerland; 3Institute of Genetics, Vetsuisse Faculty, University of Bern, Switzerland; 4GenPhyse, INRA, INPT, ENVT, Université de Toulouse, France; 5Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Switzerland; 6Division of Clinical Radiology, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Switzerland
Email: alexander.grahofer@usys.ethz.ch
Introduction Unilateral and bilateral palatoschisis or cleft palate is a well-known congenital anomaly of craniofacial development in several animal species including pigs. Only limited information regarding the occurrence of palatoschisis or cleft palate in the pig population is available. Commonly, the affected piglets die within the first days of life due to the aspiration of colostrum or milk into the lungs and consequential associated complications. Little is known about its aetiology. Nevertheless, environmental and genetic factors have been described. The aim of this study was to apply recently improved genomic resources in pigs to evaluate a possible genetic cause for the occurrence of several piglets with palatoschisis in the progeny of a single boar. Furthermore, the effect on the litter size was analysed.
Materials and Methods Due to congenital anomalies in piglets on a satellite farrowing farm in Switzerland, further investigation were conducted to evaluate the possible cause for the palatoschisis (Figure 1) in the piglets. Six litters were analyzed in detailed and further samples were obtained from the farmer. In total twenty affected piglets were used in this study.
Results In these six litters a significant decrease (p-value: 0.0055) in total born piglets (14.7 (SD ± 0.9) to 9.7 (SD± 2.7)) and an increase of stillborn piglets (0.8 (SD ± 0.6) to 1.7(SD ± 1.2)) compared with the former litters was noticed in the affected litters (Table 1). A detailed description of the phenotype was derived from necropsy and by computed tomography revealing that all 20 cases also exhibited palatoschisis and renal cysts. Furthermore, a genetic origin was assumed due to dominant inheritance as all 20 recorded cases were confirmed offspring of a single boar. The boar, which sired the malformed piglets, carried a balanced translocation between Mb-sized segments of chromosome 8 and 14. This had not been previously observed during karyotyping. All affected offspring were shown to be carriers of a partial trisomy of chromosome 14 including the FGFR2 gene, which is associated with various dominant inherited craniofacial dysostosis syndromes in man, and partial monosomy of chromosome 8 containing MSX1 known to be associated with tooth agenesis and orofacial clefts in other species.
Table 1 Reproductive parameters of six affected litters with malformed piglets in comparison with previous records of the sows.
Figure 1 Bilateral palatoschisis in a piglet
Conclusions In this report, a significant reduction in litter size of the affected litters was detected from the identified sire. Due to the extensive use of artificial insemination in the pig industry, an affected boar can cause tremendous economic losses in pig production.
Therefore, the detection of a reciprocal translocation in a boar with recently established genomic resources at an early stage is essential.
Entropion in Swiss White Alpine sheep is associated with the CTNND1 gene region on chromosome 15
N. Hirter1, A. Letko1, I. Häfliger1, D. Greber2 and C. Drögemüller11Institute of Genetics, Vetsuisse Faculty, University of Bern, Switzerland; 2Clinic for Ruminants, Vetsuisse Faculty, University of Bern, Switzerland
Email: nathalie.hirter@vetsuisse.unibe.ch
Introduction Entropion is a known congenital disorder in different species including sheep. Lambs with entropion have an inward rolling of one or both lower eyelids since birth. The inward looking eyelashes and hairs lead to a constant irritation of the cornea and, in extreme cases, to blindness. In Switzerland, a recent survey showed that the most affected Swiss White Alpine sheep (SWA) breed showed a prevalence of entropion about 6%1. Entropion in sheep is supposed to be heritable; however, so far no causative genetic variant causing this disease phenotype has been identified. The aim of the present study was to discover the genetic cause of this disease.
Materials and Methods EDTA-Blood samples were collected in more than 400 sheep in the breeds SWA and Texel (TEX) and their crossbreeds. 150 (89 cases, 61 controls) of them were genotyped using the ovine high-density 600k SNP array, and a genome-wide association study (GWAS) was performed. The genomes of two pairs of affected and normal full sibs of SWA, a single affected SWA, and a case-control full sib pair of Texel sheep were sequenced and used for disease-associated variant filtering.
Results An associated genome region on chromosome 15 was identified with entropion. The best-associated marker (p-value: 1.95 E-09) was located close to the CTNND1 gene encoding catenin delta-1. In human, recent studies have identified pathogenic variants in CTNND1 in blepharocheilodontic syndrome 2, a rare autosomal dominant disorder characterized by eyelid anomalies. After filtering for disease-associated variants in the region around gene CTNND1 using control genomes of other unrelated sheep breeds, we found two intronic single nucleotide variants and one missense variant in the CTNND1 gene. Genotyping of more than 300 sheep with known phenotypes showed no association of these three variants with entropion in SWA sheep.
Figure 1 Genome-wide association study, presented in Manhattan plot, with genome-wide significance threshold (red line = Bonferroni line)
Conclusions In conclusion, this study revealed a single locus associated with entropion in Swiss White Alpine sheep. Further sequence analysis is needed to identify the causative variant.
References
Greber D, Doherr M, Drögemüller C, Steiner A: Occurrence of congenital disorders in Swiss sheep. 2013
Session 08: Impact of animal genetics on animal health and disease
Heritability and phenotypic correlations of protein efficiency in a Swiss Large White pig population
C. Kasper, I. Ruiz-Ascacibar, P. Stoll and G. BeeAgroscope, La Tioleyre 4, 1725 Posieux, Switzerland Email : claudia.kasper-voelkl@agroscope.admin.ch
Introduction Pig production contributes importantly to environmental pollution through the emission of nitrogen waste. Many countries cannot meet the plant-protein demand of livestock with current feed cultivation practices, and an important part of high-quality protein feed, most importantly soybean meal, is imported from South America. The high global demand for protein results in an increased competition of agricultural land for human food and animal feed and ultimately to the large-scale loss of ecological habitats. It is therefore desirable to improve protein efficiency, i.e. the proportion of dietary protein that is fixed in the body, of pigs, an important livestock species, through selective breeding. However, little is known about the inheritance pattern and genetic architecture of protein efficiency as well as the genes underlying protein efficiency and their functions, which is essential for assessing the potential to breed pigs with higher protein efficiency.
Materials and Methods We used data of 294 offspring of 17 sires and 56 dams from previous experiments (Ruiz-Ascacibar et al., 2017). Nitrogen (~protein) efficiency of the empty body (NEffEB) and of the carcass (NEffCarc) were the proportion of fixed protein in the entire body and the carcass, respectively, from the total dietary protein intake. We estimated the genetic (h2) and environmental variance components (CE2) of NEffEB and NEffCarc using a mixed-effect Gaussian animal model (Henderson, 1984) following a Bayesian framework (Hadfield, 2010). We assessed phenotypic correlations of NEffEB with phosphorus efficiency, water, raw ash and fat content of the empty body of a subset (N=73) for which this information was available. The correlation of NEffEB with the number of days slaughtering was delayed because a pig did not reach the target body weight was calculated for the entire dataset.
Results The heritability of N efficiency of the empty body was higher than the one of the carcass (ℎ𝑁𝐸𝑓𝑓𝐸𝐵2 = 0.32 [0.15, 0.59] and ℎ𝑁𝐸𝑓𝑓𝐶𝑎𝑟𝑐2 = 0.16 [0.08, 0.41]) (Fig. 1). The common environment also contributed to the phenotypic variation in NEffEB (𝐶𝐸2= 0.13 [0.08, 0.27]) and NEffCarc (𝐶𝐸2= 0.16 [0.09, 0.25]). We found a low negative phenotypic correlation of NEffEB and the number of days an animal was delayed in reaching target weight (Table 1). NEffEB correlated moderately positively with phosphorus efficiency. Body composition traits (water/crude ash/crude fat content) were not correlated with NEffEB.
Table 1 Correlations of NEffEB with traits of potential economic and ecological impact as well as with body composition.
trait type coefficient ± 95% CI days delayed Spearman 𝜌 = −0.16 [−0.26, −0.07]
P efficiency Pearson 𝑟 = 0.65 [0.48, 0.77]
water content Pearson 𝑟 = −0.07 [−0.32, 0.18]
crude ash content Pearson 𝑟 = −0.16 [−0.39, 0.09]
crude fat content Pearson 𝑟 = −0.14 [−0.38, 0.11]
Figure 1 Heritability (h2, blue), common environment effect (CE2, green) and residual variance (r2, red) of protein efficiency of the whole body (A) and protein efficiency of the carcass (B).
Posterior distributions of the respective variance components (upper part), points representing single estimates are shown together with a box plot (with median, interqartile range and 5th to 95th percentile range).
Conclusions Our preliminary results indicate a potential for selective breeding towards increased protein efficiency but more research is needed to improve estimates of genetic parameters. Information on the association of genetic loci (SNPs) and protein efficiency will help understand the genes and their functions that underlie protein efficiency. We found no major trade-offs with other economically important traits. Breeding for increased protein efficiency could lead to a slower growth of the animals, but the decrease is expected to be small and might be offset by lower costs of protein-reduced feed. However, potential trade-offs with fertility, aggression and meat quality should be addressed by future studies. A reduction of proteins in pig feed can potentially facilitate both conventional and organic pig production in Switzerland.
References
Hadfield, J.D., 2010. MCMC Methods for Multi-Response Generalized Linear Mixed Models: The MCMCglmm R Package. J. Stat. Softw. 33.
https://doi.org/10.18637/jss.v033.i02
Henderson C.R., 1984. Applications of Linear Models in Animal Breeding. University of Guelph, Guelph, CA, 462 pages
Ruiz-Ascacibar, I., Stoll, P., Kreuzer, M., Boillat, V., Spring, P., Bee, G., 2017. Impact of amino acid and CP restriction from 20 to 140 kg BW on performance and dynamics in empty body protein and lipid deposition of entire male, castrated and female pigs. animal 11, 394–404. https://doi.org/10.1017/S1751731116001634
The
APOB loss-of-function mutation of Holstein dairy cattle reduces the capacities for cholesterol transport incirculation but does not imply a cholesterol deficiency
J. J. Gross1, A.-C. Schwinn1, F. Schmitz-Hsu3, A. Barenco4, T. F.-O. Neuenschwander5, C. Drögemüller2 and R. M. Bruckmaier1
1Veterinary Physiology, Vetsuisse Faculty, University of Bern, Switzerland; 2Institute of Genetics, Vetsuisse Faculty, University of Bern, Switzerland; 3Swissgenetics, Zollikofen, Switzerland; 4swissherdbook, Zollikofen, Switzerland; 5Holstein Switzerland, Posieux, Switzerland
Email: rupert.bruckmaier@vetsuisse.unibe.ch
Introduction The loss-of-function mutation of the apolipoprotein (APO) B gene in Holstein cattle accounts for increased losses in calves that are homozygous for this mutation. Heterozygous carriers of the APOB mutation are supposed to be clinically healthy, but show decreased plasma concentrations of cholesterol and lipoproteins. So far the metabolic effects of the mutation had only been investigated in heterozygous calves, bulls, and non-lactating females. In high yielding dairy cows, a marked decrease in plasma cholesterol concentration during early lactation is part of the usual metabolic changes. Given the essential role of cholesterol in fatty acid and lipid metabolism, a specific impact of the APOB mutation on metabolism and performance in dairy cows is expected.
Therefore, the aim of the present study was to investigate the effects of different APOB genotypes on metabolic parameters, hepatic metabolism, lactation and reproductive performance.
Materials and Methods Twenty pairs of full siblings with similar age, performance, and calving were investigated. Both animals of each pair were kept on the same farm and consisted of a heterozygous carrier (CDC) and a non-carrier (CDF) of the APOB mutation associated with cholesterol deficiency (CD). Blood samples were taken in early (25.5 ± 4.7 days in milk) and mid-lactation (158.2 ± 11.1 days in milk; mean ± SD), and analyzed for non-esterified fatty acids, β-hydroxybutyrate, glucose, insulin-like growth factor-1, aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) activity, total cholesterol, free cholesterol, triglycerides (TAG), high density lipoprotein-cholesterol, and phospholipids (PL). The evaluation of milk production, milk gross composition, and lactation persistency was based on official DHIA recordings.
Results Milk production and milk composition (i.e., contents of milk fat, protein, lactose, and urea) did not differ between the cows with different APOB-genotypes. Furthermore, cumulative milk production at 100, 200, and 305 DIM, and average milk fat and protein content during these intervals did not differ between CDC and CDF cows. Lactation persistency of milk production and the interval between parturition until successful conception were similar across cows of both genotypes.
Cholesterol and lipoprotein concentrations were lower in CDC compared with CDF in early and mid-lactation (P < 0.05). Metabolic parameters, and plasma TAG concentration did not differ between CDC and CDF.
Conclusions Cholesterol and lipoprotein concentrations were markedly lowered in Holstein cows heterozygous for the APOB mutation compared with non-carriers. The effect of the APOB mutation on the phenotypic expression of circulating cholesterol was persistent throughout the lactation in heterozygous carriers. However, animal health, lactational, and reproductive performance were not impaired compared with non-carriers. Parameters related to the intermediary energy metabolism were not affected by the mutation indicating that metabolic adaptations are successful and do not provoke a higher incidence of metabolic disorders. The low cholesterol concentrations associated with the APOB mutation are not due to a primary deficiency of cholesterol, as the term “cholesterol deficiency” suggests, but are rather a consequence of reduced capacities for transport in circulation. Our results indicate no need for eradication of APOB carriers from production. However, risk-matings of carriers should be avoided.