Genomic dissection of the correlation between milk yield and various health traits using functional and evolutionary information about imputed sequence variants of 34,497 German Holstein cows.

BACKGROUND: Over the last decades, it was subject of many studies to investigate the genomic connection of milk production and health traits in dairy cattle. Thereby, incorporating functional information in genomic analyses has been shown to improve the understanding of biological and molecular mechanisms shaping complex traits and the accuracies of genomic prediction, especially in small populations and across-breed settings. Still, little is known about the contribution of different functional and evolutionary genome partitioning subsets to milk production and dairy health. Thus, we performed a uni- and a bivariate analysis of milk yield (MY) and eight health traits using a set of ~34,497 German Holstein cows with 50K chip genotypes and ~17 million imputed sequence variants divided into 27 subsets depending on their functional and evolutionary annotation. In the bivariate analysis, eight trait-combinations were observed that contrasted MY with each health trait. Two genomic relationship matrices (GRM) were included, one consisting of the 50K chip variants and one consisting of each set of subset variants, to obtain subset heritabilities and genetic correlations. In addition, 50K chip heritabilities and genetic correlations were estimated applying merely the 50K GRM. RESULTS: In general, 50K chip heritabilities were larger than the subset heritabilities. The largest heritabilities were found for MY, which was 0.4358 for the 50K and 0.2757 for the subset heritabilities. Whereas all 50K genetic correlations were negative, subset genetic correlations were both, positive and negative (ranging from -0.9324 between MY and mastitis to 0.6662 between MY and digital dermatitis). The subsets containing variants which were annotated as noncoding related, splice sites, untranslated regions, metabolic quantitative trait loci, and young variants ranked highest in terms of their contribution to the traits` genetic variance. We were able to show that linkage disequilibrium between subset variants and adjacent variants did not cause these subsets` high effect. CONCLUSION: Our results confirm the connection of milk production and health traits in dairy cattle via the animals` metabolic state. In addition, they highlight the potential of including functional information in genomic analyses, which helps to dissect the extent and direction of the observed traits` connection in more detail.

Simulation of dual-purpose chicken breeding programs implementing gene editing.

BACKGROUND: In spite of being controversial and raising ethical concerns, the application of gene editing is more likely to be accepted when it contributes to improving animal welfare. One of the animal welfare and ethical issues in chicken breeding is chick culling, the killing of the male layer chicks after hatching due to the poor fattening performance. Although establishing dual-purpose chicken lines could solve this problem, unfavorable genetic correlations between egg and meat production traits hindered their competitiveness. Although it is also controversial in ethical terms, gene editing may accelerate genetic progress in dual-purpose chicken and alleviate the ethical concerns from chick culling. RESULTS: The simulation compared the utility improvement in dual-purpose use under two breeding schemes: one consisting in the improvement of the laying hens, and the second in the improvement of a synthetic line obtained from a layer broiler cross. In each breeding scheme, the breeding programs were simulated with and without gene editing. Polygenic breeding values and 500 simulated quantitative trait loci (QTL) with different levels of pleiotropy caused negative correlations between egg production, meat production, and overall health. The results of the simulation demonstrated that genetic gain could be accelerated by at most 81% for several generations if gene editing was used. The actual increase in genetic gain depended on the number of single nucleotide polymorphisms (SNPs) being edited per animal. The rate of genetic improvement became equal in scenarios with and without gene editing after 20 generations. This is because the remaining segregating QTL had small effects and their edition would have negative overall health effects from potential off-target edits. Although gene editing can improve genetic gain in quantitative traits, it can only be recommended as long as QTL with reasonable effect sizes are segregating and detectable. CONCLUSIONS: This simulation demonstrates the potential of gene editing to accelerate the simultaneous improvement of negatively correlated traits. When the risk of negative consequences from gene editing persists, the number of SNPs to be edited should be chosen carefully to obtain the optimal genetic gain.

Mendelian randomization analysis of 34,497 German Holstein cows to infer causal associations between milk production and health traits.

BACKGROUND: Claw diseases and mastitis represent the most important health issues in dairy cattle with a frequently mentioned connection to milk production. Although many studies have aimed at investigating this connection in more detail by estimating genetic correlations, they do not provide information about causality. An alternative is to carry out Mendelian randomization (MR) studies using genetic variants to investigate the effect of an exposure on an outcome trait mediated by genetic variants. No study has yet investigated the causal association of milk yield (MY) with health traits in dairy cattle. Hence, we performed a MR analysis of MY and seven health traits using imputed whole-genome sequence data from 34,497 German Holstein cows. We applied a method that uses summary statistics and removes horizontal pleiotropic variants (having an effect on both traits), which improves the power and unbiasedness of MR studies. In addition, genetic correlations between MY and each health trait were estimated to compare them with the estimates of causal effects that we expected. RESULTS: All genetic correlations between MY and each health trait were negative, ranging from - 0.303 (mastitis) to - 0.019 (digital dermatitis), which indicates a reduced health status as MY increases. The only non-significant correlation was between MY and digital dermatitis. In addition, each causal association was negative, ranging from - 0.131 (mastitis) to - 0.034 (laminitis), but the number of significant associations was reduced to five nominal and two experiment-wide significant results. The latter were between MY and mastitis and between MY and digital phlegmon. Horizontal pleiotropic variants were identified for mastitis, digital dermatitis and digital phlegmon. They were located within or nearby variants that were previously reported to have a horizontal pleiotropic effect, e.g., on milk production and somatic cell count. CONCLUSIONS: Our results confirm the known negative genetic connection between health traits and MY in dairy cattle. In addition, they provide new information about causality, which for example points to the negative energy balance mediating the connection between these traits. This knowledge helps to better understand whether the negative genetic correlation is based on pleiotropy, linkage between causal variants for both trait complexes, or indeed on a causal association.

Economic benefits of herd genotyping and using sexed semen for pure and beef-on-dairy breeding in dairy herds.

The cost benefits of herd genotyping and the benefits of using sexed semen have been affected by recent improvements in sexing technologies, incorporation of direct health traits in the German total merit index for Holstein cattle, deteriorating prices for purebred heifer calves and bull calves, and introduction of herd genotyping programs. Inseminating genetically superior dams with female-sexed Holstein semen increases the mean breeding value of heifer calves and can produce more Holstein heifer calves than are needed for replacement. This provides an opportunity to increase the selection response in health and production traits at the farm level. A deterministic model is introduced that predicts the increase or decrease in net profit when a farmer takes part in a herd genotyping program and follows a certain insemination strategy. The types of semen allocated to cows and heifers may be sexed or unsexed and Holstein or beef breed. Genetically superior heifers and cows are inseminated with female-sexed Holstein semen, intermediate dams with unsexed Holstein semen, and genetically inferior dams with unsexed or male-sexed beef breed semen. In general, participating in a herd genotyping program is beneficial for German Holstein breeders. The optimum proportions of cows and heifers that should be inseminated with a certain type of semen are sensitive to farm-specific peculiarities. A small price difference between crossbred bull calves and crossbred heifer calves often makes the use of male-sexed beef breed semen uneconomic. Under the conditions considered, it was found to be advantageous to inseminate approximately 50% of heifers and 10% of cows with the highest genetic merit with female-sexed Holstein semen. The optimum proportion of cows that should be inseminated with unsexed beef breed semen was found to be approximately 40%. In a herd with a low replacement rate, the selected heifers can exhibit their genetic superiority over a longer period of time, and a larger proportion of cows can be inseminated with beef breed semen. Participation in a herd genotyping program is, therefore, particularly beneficial for herds with low replacement rates.

Genomic analyses of nitrogen utilization efficiency, its indicator trait blood urea nitrogen and the relationship to classical growth performance and feed efficiency traits in a Landrace × Piétrain crossbred population.

Improving the nutrient efficiency in pork production is required to reduce the resource competition between human food and animal feed regarding diet components edible for humans and to minimize emissions relevant to climate or the environment. Thereby, protein utilization efficiency and its equivalent nitrogen utilization efficiency (NUE) play a major role. Breeding for more nitrogen (N) efficient pigs bears a promising strategy to improve such traits, however, directly phenotyping NUE based on N balance data is neither cost-efficient nor straightforward and not applicable for routine evaluations. Blood urea nitrogen (BUN) levels in the pig are suitable to predict the NUE and, therefore, might be an indicator trait for NUE because BUN is a relatively easy-to-measure trait. This study investigated the suitability of NUE as a selection trait in future breeding programs. The relationships to classical growth performance and feed efficiency traits were analysed as well as the relationship to BUN to infer the role of BUN as an indicator trait to improve NUE via breeding. The analyzes were based on a Landrace F1 cross population consisting of 502 individuals who descended from 20 Piétrain sires. All animals were genotyped for 48,525 SNPs. They were phenotyped in two different fattening phases, i.e., FP1 and FP2, during the experiment. Uni- and bivariate analyses were run to estimate variance components and to determine the genetic correlation between different traits or between the same trait measured at different time points. Moderate heritabilities were estimated for all traits, whereby the heritability for NUE was h2 = 0.293 in FP1 and h2 = 0.163 in FP2 and BUN had the by far highest heritability (h2 = 0.415 in FP1 and h2 = 0.460 in FP2). The significant genetic correlation between NUE and BUN showed the potential of BUN to be considered an indicator trait for NUE. This was particularly pronounced when NUE was measured in FP1 (genetic correlations r g = - 0.631 $$ {r}_g=-0.631 $$ and r g = - 0.688 $$ {r}_g=-0.688 $$ between NUE and BUN measured in FP1 and FP2, respectively). The genetic correlations of NUE and BUN with important production traits suggest selecting pigs with high growth rates and low BUN levels to breed more efficient pigs in future breeding programs.

Structural variation and eQTL analysis in two experimental populations of chickens divergently selected for feather-pecking behavior.

Feather pecking (FP) is a damaging nonaggressive behavior in laying hens with a heritable component. Its occurrence has been linked to the immune system, the circadian clock, and foraging behavior. Furthermore, dysregulation of miRNA biogenesis, disturbance of the gamma-aminobutyric acid (GABAergic) system, as well as neurodevelopmental deficiencies are currently under debate as factors influencing the propensity for FP behavior. Past studies, which focused on the dissection of the genetic factors involved in FP, relied on single nucleotide polymorphisms (SNPs) and short insertions and deletions < 50 bp (InDels). These variant classes only represent a certain fraction of the genetic variation of an organism. Hence, we reanalyzed whole-genome sequencing data from two experimental populations, which have been divergently selected for FP behavior for over more than 15 generations, performed variant calling for structural variants (SVs) as well as tandem repeats (TRs), and jointly analyzed the data with SNPs and InDels. Genotype imputation and subsequent genome-wide association studies, in combination with expression quantitative trait loci analysis, led to the discovery of multiple variants influencing the GABAergic system. These include a significantly associated TR downstream of the GABA receptor subunit beta-3 (GABRB3) gene, two microRNAs targeting several GABA receptor genes, and dystrophin (DMD), a direct regulator of GABA receptor clustering. Furthermore, we found the transcription factor ETV1 to be associated with the differential expression of 23 genes, which points toward a role of ETV1, together with SMAD4 and KLF14, in the disturbed neurodevelopment of high-feather pecking chickens.

Defining valid breeding goals for animal breeds.

BACKGROUND: The objective of any valid breeding program is to increase the suitability of a breed for its future purposes. The approach most often followed in animal breeding for optimizing breeding goals assumes that the sole desire of the owners is profit maximization. As this assumption is often violated, a generalized approach is needed that does not rely on this assumption. RESULTS: The generalized approach is based on the niche concept. The niche of a breed is a set of environments in which a small population of the breed would have a positive population growth rate. Its growth rate depends on demand from prospective consumers and supply from producers. The approach involves defining the niche that is envisaged for the breed and identifying the trait optima that maximize the breed's adaptation to its envisaged niche within the set of permissible breeding goals. The set of permissible breeding goals is the set of all potential breeding goals that are compatible with animal welfare and could be reached within the planning horizon of the breeding program. In general, the breed's adaptation depends on the satisfaction of the producers with the animals and on the satisfaction of the consumers with the products produced by the animals. When consumers buy live animals, then the breed needs to adapt to both the environments provided by the producers, and the environments provided by the consumers. The profit function is replaced by a more general adaptedness function that measures the breed's adaptation to its envisaged niche. CONCLUSIONS: The proposed approach coincides with the traditional approach if the producers have the sole desire to maximize their income, and if consumer preferences are well reflected by the product prices. If these assumptions are not met, then the traditional approach to breeding goal optimization is unlikely to result in a valid breeding goal. Using the example of companion breeds, this paper shows that the proposed approach has the potential to fill the gap.

Genomic regions underlying positive selection in local, Alpine cattle breeds.

We used genome-wide SNP data from 18 local cattle breeds from six countries of the Alpine region to characterize population structure and identify genomic regions underlying positive selection. The geographically close breeds Evolèner, Eringer, Valdostana Pezzata Nera, and Valdostana Castana were found to differ from all other Alpine breeds. In addition, three breeds, Simmental, and Original Braunvieh from Switzerland and Pinzgauer from Austria built three separate clusters. Of the 18 breeds studied, the intra-alpine Swiss breed Evolèner had the highest average inbreeding based on runs of homozygosity (FROH ) and the highest average genomic relationship within the breed. In contrast, Slovenian Cika cattle had the lowest average genomic inbreeding and the lowest average genomic relationship within the breed. We found selection signatures on chromosome 6 near known genes such as KIT and LCORL explaining variation in coat color and body size in cattle. The most prominent selection signatures were similar regardless of marker density and the breeds in the data set. In addition, using available high-density SNP data from 14 of the breeds we identified 47 genome regions as ROH islands. The proportion of homozygous animals was higher in all studied animals of local breeds than in Holstein and Brown Swiss cattle, the two most important commercial breeds in the Alpine region. We report ROH islands near genes related to thermoregulation, coat color, production, and stature. The results of this study serve as a basis for the search for causal variants underlying adaptation to the alpine environment and other specific characteristics selected during the evolution of local Alpine cattle breeds.

Genetic analysis of production traits and body size measurements and their relationships with metabolic diseases in German Holstein cattle.

This study sheds light on the genetic complexity and interplay of production, body size, and metabolic health in dairy cattle. Phenotypes for body size-related traits from conformation classification (130,166 animals) and production (101,562 animals) of primiparous German Holstein cows were available. Additionally, 21,992, 16,641, and 7,096 animals were from herds with recordings of the metabolic diseases ketosis, displaced abomasum, and milk fever in first, second, and third lactation. Moreover, all animals were genotyped. Heritabilities of traits and genetic correlations between all traits were estimated and GWAS were performed. Heritability was between 0.240 and 0.333 for production and between 0.149 and 0.368 for body size traits. Metabolic diseases were lowly heritable, with estimates ranging from 0.011 to 0.029 in primiparous cows, from 0.008 to 0.031 in second lactation, and from 0.037 to 0.052 in third lactation. Production was found to have negative genetic correlations with body condition score (BCS; -0.279 to -0.343) and udder depth (-0.348 to -0.419). Positive correlations were observed for production and body depth (0.138-0.228), dairy character (DCH) (0.334-0.422), and stature (STAT) (0.084-0.158). In first parity cows, metabolic disease traits were unfavorably correlated with production, with genetic correlations varying from 0.111 to 0.224, implying that higher yielding cows have more metabolic problems. Genetic correlations of disease traits in second and third lactation with production in primiparous cows were low to moderate and in most cases unfavorable. While BCS was negatively correlated with metabolic diseases (-0.255 to -0.470), positive correlations were found between disease traits and DCH (0.269-0.469) as well as STAT (0.172-0.242). Thus, the results indicate that larger and sharper animals with low BCS are more susceptible to metabolic disorders. Genome-wide association studies revealed several significantly associated SNPs for production and conformation traits, confirming previous findings from literature. Moreover, for production and conformation traits, shared significant signals on Bos taurus autosome (BTA) 5 (88.36 Mb) and BTA 6 (86.40 to 87.27 Mb) were found, implying pleiotropy. Additionally, significant SNPs were observed for metabolic diseases on BTA 3, 10, 14, 17, and 26 in first lactation and on BTA 2, 6, 8, 17, and 23 in third lactation. Overall, this study provides important insights into the genetic basis and interrelations of relevant traits in today's Holstein cattle breeding programs, and findings may help to improve selection decisions.

A genomic assessment of the correlation between milk production traits and claw and udder health traits in Holstein dairy cattle.

Claw diseases and mastitis represent the most important disease traits in dairy cattle with increasing incidences and a frequently mentioned connection to milk yield. Yet, many studies aimed to detect the genetic background of both trait complexes via fine-mapping of quantitative trait loci. However, little is known about genomic regions that simultaneously affect milk production and disease traits. For this purpose, several tools to detect local genetic correlations have been developed. In this study, we attempted a detailed analysis of milk production and disease traits as well as their interrelationship using a sample of 34,497 50K genotyped German Holstein cows with milk production and claw and udder disease traits records. We performed a pedigree-based quantitative genetic analysis to estimate heritabilities and genetic correlations. Additionally, we generated GWAS summary statistics, paying special attention to genomic inflation, and used these data to identify shared genomic regions, which affect various trait combinations. The heritability on the liability scale of the disease traits was low, between 0.02 for laminitis and 0.19 for interdigital hyperplasia. The heritabilities for milk production traits were higher (between 0.27 for milk energy yield and 0.48 for fat-protein ratio). Global genetic correlations indicate the shared genetic effect between milk production and disease traits on a whole genome level. Most of these estimates were not significantly different from zero, only mastitis showed a positive one to milk (0.18) and milk energy yield (0.13), as well as a negative one to fat-protein ratio (-0.07). The genomic analysis revealed significant SNPs for milk production traits that were enriched on Bos taurus autosome 5, 6, and 14. For digital dermatitis, we found significant hits, predominantly on Bos taurus autosome 5, 10, 22, and 23, whereas we did not find significantly trait-associated SNPs for the other disease traits. Our results confirm the known genetic background of disease and milk production traits. We further detected 13 regions that harbor strong concordant effects on a trait combination of milk production and disease traits. This detailed investigation of genetic correlations reveals additional knowledge about the localization of regions with shared genetic effects on these trait complexes, which in turn enables a better understanding of the underlying biological pathways and putatively the utilization for a more precise design of breeding schemes.

Genomic dominance variance analysis of health and milk production traits in German Holstein cattle.

Genomic analyses commonly explore the additive genetic variance of traits. The non-additive variance, however, is usually small but often significant in dairy cattle. This study aimed at dissecting the genetic variance of eight health traits that recently entered the total merit index in Germany and the somatic cell score (SCS), as well as four milk production traits by analysing additive and dominance variance components. The heritabilities were low for all health traits (between 0.033 for mastitis and 0.099 for SCS), and moderate for the milk production traits (between 0.261 for milk energy yield and 0.351 for milk yield). For all traits, the contribution of dominance variance to the phenotypic variance was low, varying between 0.018 for ovarian cysts and 0.078 for milk yield. Inbreeding depression, inferred from the SNP-based observed homozygosity, was significant only for the milk production traits. The contribution of dominance variance to the genetic variance was larger for the health traits, ranging from 0.233 for ovarian cysts to 0.551 for mastitis, encouraging further studies that aim at discovering QTLs based on their additive and dominance effects.

Genomic rotational crossbreeding with advanced optimum contribution selection methods applied to simulated German Angler and German Holstein dairy cattle populations.

Many local dairy cattle breeds are facing genetic extinction due to a large proportion of foreign genes, which have been introgressed in the past. In addition, the performance gap to popular high-yielding breeds is increasing, resulting in a risk of numeric extinction. In the present simulation study, a genomic rotational crossbreeding scheme with the high-yielding German Holstein breed and the numerically small German Angler breed was analysed with the aim to utilize heterosis effects in the crossbred animals. Simultaneously inbreeding was controlled, and the amount of Holstein introgression observed in the Angler breed was reduced. Different scenarios of implementing OCS methods for Angler individuals were evaluated, which differed in their restrictions regarding kinship, native kinship, as well as the amount of genetic contributions from German Holstein. The results showed that rotational crossbreeding can result in superior crossbred offspring compared to the purebred parental lines, whereby OCS methods can simultaneously restrict the increase in inbreeding and keep the Holstein contributions at their current level. However, reducing the amount of migrant contributions while restricting the increase in the native kinship in Angler turned out to be a costly restriction. The reason was that Angler with low genetic contributions from Holsteins tended to have similar Angler ancestors. Consequently, reducing Holstein contributions would considerably increase the native kinship in Angler if it were not constrained. The constraint on the native kinship made a constraint on the conventional kinship superfluous and caused it to increase at a much lower rate than envisaged. This led to both, a high genetic diversity and a low genetic gain. The high genetic diversity in Angler also resulted in lower and oscillating heterosis effects in the crossbred animals. Thus, the reduction of migrant contribution did not increase heterosis effects in the crossbred offspring, and did not result in superior crossbred offspring in general.

Genetic and non-genetic factors influencing KLH binding natural antibodies and specific antibody response to Newcastle disease in Kenyan chicken populations.

This study aimed at investigating the influence of genetic and non-genetic factors on immune traits to inform on possibilities of genetic improvement of disease resistance traits in local chicken of Kenya. Immune traits such as natural and specific antibodies are considered suitable indicators of an individual's health status and consequently, used as indicator traits of disease resistance. In this study, natural antibodies binding to Keyhole Limpet Hemocyanin (KLH-NAbs) was used to measure general disease resistance. Specific antibodies binding to Newcastle disease virus (NDV-IgG) post vaccination was used to measure specific disease resistance. Titers of KLH-NAbs isotypes (KLH-IgM, KLH-IgG and KLH-IgA) and NDV-IgG were measured in 1,540 chickens of different ages ranging from 12 to 56 weeks. A general linear model was fitted to determine the effect of sex, generation, population type, phylogenetic cluster, line, genotype and age on the antibody traits. A multivariate animal mixed model was fitted to estimate heritability and genetic correlations among the antibody traits. The model constituted of non-genetic factors found to have a significant influence on the antibody traits as fixed effects, and animal and residual effects as random variables. Overall mean (±SE) concentration levels for KLH-IgM, KLH-IgG, KLH-IgA and NDV-IgG were 10.33 ± 0.04, 9.08 ± 0.02, 6.00 ± 0.02 and 10.12 ± 0.03, respectively. Sex, generation and age (linear covariate) significantly (p < 0.05) influenced variation across all the antibody traits. Genotype effects (p < 0.05) were present in all antibody traits, apart from KLH-IgA. Interaction between generation and line was significant (p < 0.05) in KLH-IgM and NDV-IgG while nesting phylogenetic cluster within population significantly (p < 0.05) influenced all antibody traits, apart from KLH-IgA. Heritability estimates for KLH-IgM, KLH-IgG, KLH-IgA and NDV-IgG were 0.28 ± 0.08, 0.14 ± 0.06, 0.07 ± 0.04 and 0.31 ± 0.06, respectively. There were positive genetic correlations (0.40-0.61) among the KLH-NAbs while negative genetic correlations (-0.26 to -0.98) were observed between the KLH-NAbs and NDV-IgG. Results from this study indicate that non-genetic effects due to biological and environmental factors influence natural and specific antibodies and should be accounted for to reduce bias and improve accuracy when evaluating the traits. Subsequently, the moderate heritability estimates in KLH-IgM and NDV-IgG suggest selection possibilities for genetic improvement of general and specific immunity, respectively, and consequently disease resistance. However, the negative correlations between KLH-NAbs and NDV-IgG indicate the need to consider a suitable approach that can optimally combine both traits in a multiple trait selection strategies.

Structural variants and tandem repeats in the founder individuals of four F2 pig crosses and implications to F2 GWAS results.

BACKGROUND: Structural variants and tandem repeats are relevant sources of genomic variation that are not routinely analyzed in genome wide association studies mainly due to challenging identification and genotyping. Here, we profiled these variants via state-of-the-art strategies in the founder animals of four F2 pig crosses using whole-genome sequence data (20x coverage). The variants were compared at a founder level with the commonly screened SNPs and small indels. At the F2 level, we carried out an association study using imputed structural variants and tandem repeats with four growth and carcass traits followed by a comparison with a previously conducted SNPs and small indels based association study. RESULTS: A total of 13,201 high confidence structural variants and 103,730 polymorphic tandem repeats (with a repeat length of 2-20 bp) were profiled in the founders. We observed a moderate to high (r from 0.48 to 0.57) level of co-localization between SNPs or small indels and structural variants or tandem repeats. In the association step 56.56% of the significant variants were not in high LD with significantly associated SNPs and small indels identified for the same traits in the earlier study and thus presumably not tagged in case of a standard association study. For the four growth and carcass traits investigated, many of the already proposed candidate genes in our previous studies were confirmed and additional ones were identified. Interestingly, a common pattern on how structural variants or tandem repeats regulate the phenotypic traits emerged. Many of the significant variants were embedded or nearby long non-coding RNAs drawing attention to their functional importance. Through which specific mechanisms the identified long non-coding RNAs and their associated structural variants or tandem repeats contribute to quantitative trait variation will need further investigation. CONCLUSIONS: The current study provides insights into the characteristics of structural variants and tandem repeats and their role in association studies. A systematic incorporation of these variants into genome wide association studies is advised. While not of immediate interest for genomic prediction purposes, this will be particularly beneficial for elucidating biological mechanisms driving the complex trait variation.

The light response in chickens divergently selected for feather pecking behavior reveals mechanistic insights towards psychiatric disorders.

BACKGROUND: Feather pecking is a serious behavioral disorder in chickens that has a considerable impact on animal welfare and poses an economic burden for poultry farming. To study the underlying genetics of feather pecking animals were divergently selected for feather pecking over 15 generations based on estimated breeding values for the behavior. METHODS AND RESULTS: By characterizing the transcriptomes of whole brains isolated from high and low feather pecking chickens in response to light stimulation we discovered a putative dysregulation of micro RNA processing caused by a lack of Dicer1. This results in a prominent downregulation of the GABRB2 gene and other GABA receptor transcripts, which might cause a constant high level of excitation in the brains of high feather pecking chickens. Moreover, our results point towards an increase in immune system-related transcripts that may be caused by higher interferon concentrations due to Dicer1 downregulation. CONCLUSION: Based on our results, we conclude that feather pecking in chickens and schizophrenia in humans have numerous common features. For instance, a Dicer1 dependent disruption of miRNA biogenesis and the lack of GABRB2 expression have been linked to schizophrenia pathogenesis. Furthermore, disturbed circadian rhythms and dysregulation of genes involved in the immune system are common features of both conditions.

Composition of the ileum microbiota is a mediator between the host genome and phosphorus utilization and other efficiency traits in Japanese quail (Coturnix japonica).

BACKGROUND: Phosphorus is an essential nutrient in all living organisms and, currently, it is the focus of much attention due to its global scarcity, the environmental impact of phosphorus from excreta, and its low digestibility due to its storage in the form of phytates in plants. In poultry, phosphorus utilization is influenced by composition of the ileum microbiota and host genetics. In our study, we analyzed the impact of host genetics on composition of the ileum microbiota and the relationship of the relative abundance of ileal bacterial genera with phosphorus utilization and related quantitative traits in Japanese quail. An F2 cross of 758 quails was genotyped with 4k genome-wide single nucleotide polymorphisms (SNPs) and composition of the ileum microbiota was characterized using target amplicon sequencing. Heritabilities of the relative abundance of bacterial genera were estimated and quantitative trait locus (QTL) linkage mapping for the host was conducted for the heritable genera. Phenotypic and genetic correlations and recursive relationships between bacterial genera and quantitative traits were estimated using structural equation models. A genomic best linear unbiased prediction (GBLUP) and microbial (M)BLUP hologenomic selection approach was applied to assess the feasibility of breeding for improved phosphorus utilization based on the host genome and the heritable part of composition of the ileum microbiota. RESULTS: Among the 59 bacterial genera examined, 24 showed a significant heritability (nominal p ≤ 0.05), ranging from 0.04 to 0.17. For these genera, six genome-wide significant QTL were mapped. Significant recursive effects were found, which support the indirect host genetic effects on the host's quantitative traits via microbiota composition in the ileum of quail. Cross-validated microbial and genomic prediction accuracies confirmed the strong impact of microbial composition and host genetics on the host's quantitative traits, as the GBLUP accuracies based on the heritable microbiota-mediated components of the traits were similar to the accuracies of conventional GBLUP based on genome-wide SNPs. CONCLUSIONS: Our results revealed a significant effect of host genetics on composition of the ileal microbiota and confirmed that host genetics and composition of the ileum microbiota have an impact on the host's quantitative traits. This offers the possibility to breed for improved phosphorus utilization based on the host genome and the heritable part of composition of the ileum microbiota.

Analysis of the brain transcriptome in lines of laying hens divergently selected for feather pecking.

BACKGROUND: Feather pecking (FP) in laying hens reduces animal welfare and leads to economic losses for the layer industry. FP is considered a heritable condition that is influenced by dysregulation of neurotransmitter homeostasis, the gut microbiome, and the immune system. To identify genes and biological pathways responsible for FP behavior we compared the brain transcriptomes of 48 hens divergently selected for FP. In addition, we tested if high feather peckers (HFP) and low feather peckers (LFP) respond differently to light since light has been shown to trigger FP behavior. RESULTS: Of approximately 48 million reads/sample an average of 98.4% were mapped to the chicken genome (GRCg6a). We found 13,070 expressed genes in the analyzed brains of which 423 showed differential expression between HFP and LFP. Genes of uncertain function and non-coding RNAs were overrepresented among those transcripts. Functional analyses revealed the involvement of cholinergic signaling, postsynaptic activity, membrane channels, and the immune system. After the light stimulus, 28 genes were found to be differentially expressed. These included an interaction cluster of core components of the circadian clock. However, differences in the response to light between HFP and LFP were not detectable. CONCLUSIONS: Genes involved in cholinergic signaling, channel activity, synaptic transmission, and immune response were found to be involved in FP behavior. We propose a model in which the gut microbiota modulates the immune system, which in turn affects cholinergic signaling. This might have an influence on monoamine signaling with possible involvement of GABA or glutamate signaling.

Meta-analyses of genome wide association studies in lines of laying hens divergently selected for feather pecking using imputed sequence level genotypes.

BACKGROUND: Feather pecking (FP) is damaging behavior in laying hens leading to global economic losses in the layer industry and massive impairments of animal welfare. The objective of the study was to discover genetic variants and affected genes that lead to FP behavior. To achieve that we imputed low-density genotypes from two different populations of layers divergently selected for FP to sequence level by performing whole genome sequencing on founder and half-sib individuals. In order to decipher the genetic structure of FP, genome wide association studies and meta-analyses of two resource populations were carried out by focusing on the traits 'feather pecks delivered' (FPD) and the 'posterior probability of a hen to belong to the extreme feather pecking subgroup' (pEFP). RESULTS: In this meta-analysis, we discovered numerous genes that are affected by polymorphisms significantly associated with the trait FPD. Among them SPATS2L, ZEB2, KCHN8, and MRPL13 which have been previously connected to psychiatric disorders with the latter two being responsive to nicotine treatment. Gene set enrichment analysis revealed that phosphatidylinositol signaling is affected by genes identified in the GWAS and that the Golgi apparatus as well as brain structure may be involved in the development of a FP phenotype. Further, we were able to validate a previously discovered QTL for the trait pEFP on GGA1, which contains variants affecting NIPA1, KIAA1211L, AFF3, and TSGA10. CONCLUSIONS: We provide evidence for the involvement of numerous genes in the propensity to exhibit FP behavior that could aid in the selection against this unwanted trait. Furthermore, we identified variants that are involved in phosphatidylinositol signaling, Golgi metabolism and cell structure and therefore propose changes in brain structure to be an influential factor in FP, as already described in human neuropsychiatric disorders.

Selecting the hologenome to breed for an improved feed efficiency in pigs-A novel selection index.

Most traits in animal breeding, including feed efficiency traits in pigs, are affected by many genes with small effect and have a moderately high heritability between 0.1 and 0.5, which enables efficient selection. Since the microbiota composition in the gastrointestinal tract is also partly heritable and was shown to have a substantial effect on feed efficiency, the host genes affect the phenotype not only directly by altering metabolic pathways, but also indirectly by changing the microbiota composition. The effect m i of the microbiota composition on the breeding value g i of an animal i is the conditional expectation of its breeding value, given the vector φ i with microbiota frequencies, that is m i = E g i | φ i . The breeding value g i of an animal can therefore be decomposed into a heritable contribution m i that arises from an altered microbiota composition and a heritable contribution p i that arises from altered metabolic pathways within the animal, so g i = m i + p i . Instead of selecting for breeding value g ^ i , an index comprising the two components m ^ i and p ^ i with appropriate weights, that is I i = λ 1 m ^ i + λ 2 p ^ i , can be used. The present study shows how this breeding strategy can be applied in pig genomic selection breeding scheme for two feed efficiency traits and daily gain.

Ileal Transcriptome Profiles of Japanese Quail Divergent in Phosphorus Utilization.

Phosphorus (P) is an essential component for all living beings. Low P diets prompt phenotypic and molecular adaptations to maintain P homeostasis and increase P utilization (PU). Knowledge of the molecular mechanisms of PU is needed to enable targeted approaches to improve PU efficiency and thus lower P excretion in animal husbandry. In a previous population study, Japanese quail were subjected to a low P diet lacking mineral P and exogenous phytase. Individual PU was determined based on total P intake and excretion. A subset of 20 extreme siblings discordant for PU was selected to retrieve gene expression patterns of ileum (n = 10 per PU group). Sequencing reads have been successfully mapped to the current Coturnix japonica reference genome with an average mapping rate of 86%. In total, 640 genes were found to be differentially abundant between the low and high PU groups (false discovery rate ≤ 0.05). Transcriptional patterns suggest a link between improved PU and mitochondrial energy metabolism, accelerated cell proliferation of enterocytes, and gut integrity. In assessing indicators of the efficient use of macro- and micronutrients, further research on turnover and proliferation rates of intestinal cells could provide an approach to improve P efficiency in poultry species.