Low public awareness opens up new opportunities for highlighting milk as an iodine dietary source.

This international survey provides insights into public awareness of the importance of iodine as an essential trace mineral in human health along with knowledge of iodine dietary sources. The online questionnaire included sociodemographic aspects and dietary iodine consumer awareness on 7-point Likert-type questions. A total of 4,704 questionnaires from 16 countries were considered. Answers were analyzed through a multiple regression linear model including country, gender, age, education level, and employment status as fixed effects. Respondents were moderately aware of the importance of fish (4.86) and seafood (4.90) as dietary iodine sources, but less aware of milk as a primary iodine source (3.32). Respondent awareness varied considerably across countries. Age, education level, and employment status only modified their perception when asked about fish and seafood as a source of iodine, with elderly respondents, those highly educated and of working age being more aware of their relevance as dietary iodine sources. Respondent knowledge did not vary by age, education level, employment status, or gender when asked about cereals, vegetables and fruits, meat and milk as iodine-rich food sources. Consequently, labeling milk and dairy products as an iodine-rich food source should be considered. Public authorities can consider the results from this survey in promotional campaigns to improve the awareness of different iodine sources and their beneficial effect on health.

Prevalence of sex-chromosome aneuploidy estimated using SNP genotype intensity information in a large population of juvenile dairy and beef cattle.

Aneuploidy is a genetic condition characterized by the loss or gain of one or more chromosomes. Aneuploidy affecting the sex chromosomes can lead to infertility in otherwise externally phenotypically normal cattle. Early identification of cattle with sex chromosomal aneuploidy is important to minimize the costs associated with rearing infertile cattle and futile breeding attempts. As most livestock breeding programs routinely genotype their breeding populations using single nucleotide polymorphism (SNP) arrays, this study aimed to assess the feasibility of integrating an aneuploidy screening tool into the existing pipelines that handle dense SNP genotype data. A further objective was to estimate the prevalence of sex chromosome aneuploidy in a population of 146,431 juvenile cattle using available genotype intensity data. Three genotype intensity statistics were used: the LogR Ratio (LRR), R-value (the sum of X and Y SNP probe intensities), and B-allele frequency (BAF) measurements. Within the female-verified population of 124,958 individuals, the estimated prevalence rate was 0.0048% for XO, 0.0350% for XXX, and 0.0004% for XXY. The prevalence of XXY in the male-verified population was 0.0870% (i.e., 18 out of 20,670 males). Cytogenetic testing was used to verify 2 of the XXX females who were still alive. The proposed approach can be readily integrated into existing genomic pipelines, serving as an efficient, large-scale screening tool for aneuploidy. Its implementation could enable the early identification of infertile animals with sex-chromosome aneuploidy.

Understanding the underlying genetic mechanisms for age at first calving, inter-calving period and scrotal circumference in Bonsmara cattle.

BACKGROUND: Reproduction is a key feature of the sustainability of a species and thus represents an important component in livestock genetic improvement programs. Most reproductive traits are lowly heritable. In order to gain a better understanding of the underlying genetic basis of these traits, a genome-wide association was conducted for age at first calving (AFC), first inter-calving period (ICP) and scrotal circumference (SC) within the South African Bonsmara breed. Phenotypes and genotypes (120,692 single nucleotide polymorphisms (SNPs) post editing) were available on 7,128 South African Bonsmara cattle; the association analyses were undertaken using linear mixed models. RESULTS: Genomic restricted maximum likelihood analysis of the 7,128 SA Bonsmara cattle yielded genomic heritability's of 0.183 (SE = 0.021) for AFC, 0.207 (SE = 0.022) for ICP and 0.209 (SE = 0.019) for SC. A total of 16, 23 and 51 suggestive (P ≤ 4 × 10-6) SNPs were associated with AFC, ICP and SC, while 11, 11 and 44 significant (P ≤ 4 × 10-7) SNPs were associated with AFC, ICP and SC respectively. A total of 11 quantitative trait loci (QTL) and 11 candidate genes were co-located with these associated SNPs for AFC, with 10 QTL harbouring 11 candidate genes for ICP and 41 QTL containing 40 candidate genes for SC. The QTL identified were close to genes previously associated with carcass, fertility, growth and milk-related traits. The biological pathways influenced by these genes include carbohydrate catabolic processes, cellular development, iron homeostasis, lipid metabolism and storage, immune response, ovarian follicle development and the regulation of DNA transcription and RNA translation. CONCLUSIONS: This was the first attempt to study the underlying polymorphisms associated with reproduction in South African beef cattle. Genes previously reported in cattle breeds for numerous traits bar AFC, ICP or SC were detected in this study. Over 20 different genes have not been previously reported in beef cattle populations and may have been associated due to the unique genetic composite background of the SA Bonsmara breed.

Variation in the proportion of the segregating genome shared between full-sibling cattle and sheep.

The construction of covariance matrices that account for the genetic relationships among individuals, using pedigree or genotype data, is integral to genetic evaluations, which are now routinely used in the field of animal breeding. The objective of the present study was to estimate the standard deviation in the proportion of the segregating genome that is shared between pairs of full-sibling cattle and sheep independently. Post edits, genotype data comprising 46,069 autosomal single nucleotide polymorphisms (SNPs) were available for 4532 unique full-sibling sheep pairs, as well as for their respective parents. Post edits, genotypes from 50,493 autosomal SNPs were also available for 10,000 unique full-sibling cattle pairs, as well as their respective parents. Genomic relationship matrices were constructed for the sheep and cattle populations, separately. After accounting for both parental genomic inbreeding and the genomic relationship between both parents, the standard deviation in full-sibling cattle and sheep genomic relationships was 0.040 and 0.037 units, respectively. In addition, the intercept value from a linear regression model which regressed each full-sibling genomic relationship on both sire and dam inbreeding, as well as the genomic relationship between the parents, was 0.499 (0.001) for sheep and 0.500 (0.001) for cattle, conforming to the expectation that full-siblings, on average, share 50% of their segregating genome.

Characterisation of eight cattle with Swyer syndrome by whole-genome sequencing.

Swyer syndrome is where an individual has the karyotype of a typical male yet is phenotypically a female. The lack of a (functional) SRY gene located on the Y-chromosome is implicated in some cases of the Swyer syndrome, although many Swyer individuals with an apparently fully functional SRY gene have also been documented. The present study undertook whole genome sequence analyses of eight cattle with suspected Swyer syndrome and compared their genome to that of both a control male and female. Sequence analyses coupled with female phenotypes confirmed that all eight individuals had the 60,XY sex reversal Swyer syndrome. Seven of the eight Swyer syndrome individuals had a deletion on the Y chromosome encompassing the SRY gene (i.e., SRY-). The eighth individual had no obvious mutation in the SRY gene (SRY+) or indeed in any reported gene associated with sex reversal in mammals; a necropsy was performed on this individual. No testicles were detected during the necropsy. Histological examination of the reproductive tract revealed an immature uterine body and horns with inactive glandular tissue of normal histological appearance; both gonads were elongated, a characteristic of most reported cases of Swyer in mammals. The flanking sequence of 11 single nucleotide polymorphisms within 10 kb of the SRY gene are provided to help diagnose some cases of Swyer syndrome. These single nucleotide polymorphisms will not, however, detect all cases of Swyer syndrome since, as evidenced from the present study (and other studies), some individuals with the Swyer condition still contain the SRY gene (i.e., SRY+).

Historical Introgression from Wild Relatives Enhanced Climatic Adaptation and Resistance to Pneumonia in Sheep.

How animals, particularly livestock, adapt to various climates and environments over short evolutionary time is of fundamental biological interest. Further, understanding the genetic mechanisms of adaptation in indigenous livestock populations is important for designing appropriate breeding programs to cope with the impacts of changing climate. Here, we conducted a comprehensive genomic analysis of diversity, interspecies introgression, and climate-mediated selective signatures in a global sample of sheep and their wild relatives. By examining 600K and 50K genome-wide single nucleotide polymorphism data from 3,447 samples representing 111 domestic sheep populations and 403 samples from all their seven wild relatives (argali, Asiatic mouflon, European mouflon, urial, snow sheep, bighorn, and thinhorn sheep), coupled with 88 whole-genome sequences, we detected clear signals of common introgression from wild relatives into sympatric domestic populations, thereby increasing their genomic diversities. The introgressions provided beneficial genetic variants in native populations, which were significantly associated with local climatic adaptation. We observed common introgression signals of alleles in olfactory-related genes (e.g., ADCY3 and TRPV1) and the PADI gene family including in particular PADI2, which is associated with antibacterial innate immunity. Further analyses of whole-genome sequences showed that the introgressed alleles in a specific region of PADI2 (chr2: 248,302,667-248,306,614) correlate with resistance to pneumonia. We conclude that wild introgression enhanced climatic adaptation and resistance to pneumonia in sheep. This has enabled them to adapt to varying climatic and environmental conditions after domestication.

Breeding for improved protein fractions and free amino acids concentration in bovine milk.

Considerable resources are required to routinely measure detailed milk compositional traits. Hence, an insufficient volume of phenotypic data can hinder genetic progress in these traits within dairy cow breeding programmes. The objective of the present study was to quantify the opportunities for breeding for improved milk protein and free amino acid (FAA) composition by exploiting mid-infrared spectroscopy (MIRS) predictions routinely recorded from milk samples. Genetic parameters for protein fractions and FAA composition were estimated using 134,546 test-day records from 16,166 lactations on 9,572 cows using linear mixed models. Heritability of MIRS-predicted protein fractions ranged from 0.19 (α-lactalbumin) to 0.55 (ß-lactoglobulin A), while heritability of MIRS-predicted FAA ranged from 0.08 for glycine to 0.29 for glutamic acid. Genetic correlations among the MIRS-predicted FAA were moderate to strong ranging from -0.44 (aspartic acid and lysine) to 0.97 (glutamic acid and total FAA). Adjustment of the genetic correlations for the genetic merit of 24-h milk yield did not greatly affect the correlations. Results from the current study highlight the presence of exploitable genetic variation for both protein fractions and FAA in dairy cow milk. Besides, the direction of genetic correlations reveals that breeding programmes directly selecting for greater milk protein concentration carry with them favourable improvement in casein and whey fractions.

Genome-wide association analyses of carcass traits using copy number variants and raw intensity values of single nucleotide polymorphisms in cattle.

BACKGROUND: The carcass value of cattle is a function of carcass weight and quality. Given the economic importance of carcass merit to producers, it is routinely included in beef breeding objectives. A detailed understanding of the genetic variants that contribute to carcass merit is useful to maximize the efficiency of breeding for improved carcass merit. The objectives of the present study were two-fold: firstly, to perform genome-wide association analyses of carcass weight, carcass conformation, and carcass fat using copy number variant (CNV) data in a population of 923 Holstein-Friesian, 945 Charolais, and 974 Limousin bulls; and secondly to perform separate association analyses of carcass traits on the same population of cattle using the Log R ratio (LRR) values of 712,555 single nucleotide polymorphisms (SNPs). The LRR value of a SNP is a measure of the signal intensity of the SNP generated during the genotyping process. RESULTS: A total of 13,969, 3,954, and 2,805 detected CNVs were tested for association with the three carcass traits for the Holstein-Friesian, Charolais, and Limousin, respectively. The copy number of 16 CNVs and the LRR of 34 SNPs were associated with at least one of the three carcass traits in at least one of the three cattle breeds. With the exception of three SNPs, none of the quantitative trait loci detected in the CNV association analyses or the SNP LRR association analyses were also detected using traditional association analyses based on SNP allele counts. Many of the CNVs and SNPs associated with the carcass traits were located near genes related to the structure and function of the spliceosome and the ribosome; in particular, U6 which encodes a spliceosomal subunit and 5S rRNA which encodes a ribosomal subunit. CONCLUSIONS: The present study demonstrates that CNV data and SNP LRR data can be used to detect genomic regions associated with carcass traits in cattle providing information on quantitative trait loci over and above those detected using just SNP allele counts, as is the approach typically employed in genome-wide association analyses.

Integrative genomics of the mammalian alveolar macrophage response to intracellular mycobacteria.

BACKGROUND: Bovine TB (bTB), caused by infection with Mycobacterium bovis, is a major endemic disease affecting global cattle production. The key innate immune cell that first encounters the pathogen is the alveolar macrophage, previously shown to be substantially reprogrammed during intracellular infection by the pathogen. Here we use differential expression, and correlation- and interaction-based network approaches to analyse the host response to infection with M. bovis at the transcriptome level to identify core infection response pathways and gene modules. These outputs were then integrated with genome-wide association study (GWAS) data sets to enhance detection of genomic variants for susceptibility/resistance to M. bovis infection. RESULTS: The host gene expression data consisted of RNA-seq data from bovine alveolar macrophages (bAM) infected with M. bovis at 24 and 48 h post-infection (hpi) compared to non-infected control bAM. These RNA-seq data were analysed using three distinct computational pipelines to produce six separate gene sets: 1) DE genes filtered using stringent fold-change and P-value thresholds (DEG-24: 378 genes, DEG-48: 390 genes); 2) genes obtained from expression correlation networks (CON-24: 460 genes, CON-48: 416 genes); and 3) genes obtained from differential expression networks (DEN-24: 339 genes, DEN-48: 495 genes). These six gene sets were integrated with three bTB breed GWAS data sets by employing a new genomics data integration tool-gwinteR. Using GWAS summary statistics, this methodology enabled detection of 36, 102 and 921 prioritised SNPs for Charolais, Limousin and Holstein-Friesian, respectively. CONCLUSIONS: The results from the three parallel analyses showed that the three computational approaches could identify genes significantly enriched for SNPs associated with susceptibility/resistance to M. bovis infection. Results indicate distinct and significant overlap in SNP discovery, demonstrating that network-based integration of biologically relevant transcriptomics data can leverage substantial additional information from GWAS data sets. These analyses also demonstrated significant differences among breeds, with the Holstein-Friesian breed GWAS proving most useful for prioritising SNPS through data integration. Because the functional genomics data were generated using bAM from this population, this suggests that the genomic architecture of bTB resilience traits may be more breed-specific than previously assumed.

Herd solutions from genetic evaluations can be used as a tool to rescale the expected expression of genetic potential in cattle.

The objective of this study was to determine whether response to selection for carcass weight (CW), conformation (CC) and fat (CF), and the association between heterosis and carcass performance varied by herd environment in cattle. Following edits, carcass information was available for 4,616,761 cattle, of which the majority were some crossbred combination of the following breeds: Angus, Aubrac, Belgian Blue, Blonde d'Aquitaine, Charolais, Hereford, Holstein-Friesian, Jersey, Limousin, Saler, Shorthorn and Simmental. Herd environment was defined separately for each carcass trait using herd solutions outputted from carcass trait genetic evaluations. A total of 3,859 herds were stratified, for each trait, into one of five strata based on their corresponding percentile herd solution rank, with the response to selection and the effect of heterosis then estimated within each stratum. The response in CW and CC from selection on the respective estimated breeding values (EBV) increased between the lowest (0.71 kg and 0.89 CC score increase per unit increase in the respective EBV) and highest (0.99 kg and 1.25 CC score increase per unit increase in the respective EBV) corresponding herd stratum. The response in CF from selection on CF EBV, however, reduced between the lowest and highest CF herd stratum (respective increases of 0.93 and 0.83 CF scores per unit increase in CF EBV). In addition, the effect of a unit increase in heterosis coefficient on CW, CC and CF also varied by herd stratum. Furthermore, results (i.e. the area under relative operating characteristic curves) from the present study demonstrated that the response to selection and heterosis effects estimated for the different herd stratum can be used, along with EBVs and the herd solutions themselves, to improve the accuracy of phenotypic predictions. Results from the present study could help producers to make more informed breeding decisions that are bespoke to their herd.

Concordance rate between copy number variants detected using either high- or medium-density single nucleotide polymorphism genotype panels and the potential of imputing copy number variants from flanking high density single nucleotide polymorphism haplotypes in cattle.

BACKGROUND: The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) using the flanking single nucleotide polymorphism (SNP) haplotype structure in cattle. While this objective was achieved using high-density genotype panels (i.e., 713,162 SNPs), a secondary objective investigated the concordance of CNVs called with this high-density genotype panel compared to CNVs called from a medium-density panel (i.e., 45,677 SNPs in the present study). This is the first study to compare CNVs called from high-density and medium-density SNP genotypes from the same animals. High (and medium-density) genotypes were available on 991 Holstein-Friesian, 1015 Charolais, and 1394 Limousin bulls. The concordance between CNVs called from the medium-density and high-density genotypes were calculated separately for each animal. A subset of CNVs which were called from the high-density genotypes was selected for imputation. Imputation was carried out separately for each breed using a set of high-density SNPs flanking the midpoint of each CNV. A CNV was deemed to be imputed correctly when the called copy number matched the imputed copy number. RESULTS: For 97.0% of CNVs called from the high-density genotypes, the corresponding genomic position on the medium-density of the animal did not contain a called CNV. The average accuracy of imputation for CNV deletions was 0.281, with a standard deviation of 0.286. The average accuracy of imputation of the CNV normal state, i.e. the absence of a CNV, was 0.982 with a standard deviation of 0.022. Two CNV duplications were imputed in the Charolais, a single CNV duplication in the Limousins, and a single CNV duplication in the Holstein-Friesians; in all cases the CNV duplications were incorrectly imputed. CONCLUSION: The vast majority of CNVs called from the high-density genotypes were not detected using the medium-density genotypes. Furthermore, CNVs cannot be accurately predicted from flanking SNP haplotypes, at least based on the imputation algorithms routinely used in cattle, and using the SNPs currently available on the high-density genotype panel.

Genomic regions associated with muscularity in beef cattle differ in five contrasting cattle breeds.

BACKGROUND: Linear type traits, which reflect the muscular characteristics of an animal, could provide insight into how, in some cases, morphologically very different animals can yield the same carcass weight. Such variability may contribute to differences in the overall value of the carcass since primal cuts vary greatly in price; such variability may also hinder successful genome-based association studies. Therefore, the objective of our study was to identify genomic regions that are associated with five muscularity linear type traits and to determine if these significant regions are common across five different breeds. Analyses were carried out using linear mixed models on imputed whole-genome sequence data in each of the five breeds, separately. Then, the results of the within-breed analyses were used to conduct an across-breed meta-analysis per trait. RESULTS: We identified many quantitative trait loci (QTL) that are located across the whole genome and associated with each trait in each breed. The only commonality among the breeds and traits was a large-effect pleiotropic QTL on BTA2 that contained the MSTN gene, which was associated with all traits in the Charolais and Limousin breeds. Other plausible candidate genes were identified for muscularity traits including PDE1A, PPP1R1C and multiple collagen and HOXD genes. In addition, associated (gene ontology) GO terms and KEGG pathways tended to differ between breeds and between traits especially in the numerically smaller populations of Angus, Hereford, and Simmental breeds. Most of the SNPs that were associated with any of the traits were intergenic or intronic SNPs located within regulatory regions of the genome. CONCLUSIONS: The commonality between the Charolais and Limousin breeds indicates that the genetic architecture of the muscularity traits may be similar in these breeds due to their similar origins. Conversely, there were vast differences in the QTL associated with muscularity in Angus, Hereford, and Simmental. Knowledge of these differences in genetic architecture between breeds is useful to develop accurate genomic prediction equations that can operate effectively across breeds. Overall, the associated QTL differed according to trait, which suggests that breeding for a morphologically different (e.g. longer and wider versus shorter and smaller) more efficient animal may become possible in the future.

Genetic control of temperament traits across species: association of autism spectrum disorder risk genes with cattle temperament.

BACKGROUND: Temperament traits are of high importance across species. In humans, temperament or personality traits correlate with psychological traits and psychiatric disorders. In cattle, they impact animal welfare, product quality and human safety, and are therefore of direct commercial importance. We hypothesized that genetic factors that contribute to variation in temperament among individuals within a species will be shared between humans and cattle. Using imputed whole-genome sequence data from 9223 beef cattle from three cohorts, a series of genome-wide association studies was undertaken on cattle flight time, a temperament phenotype measured as the time taken for an animal to cover a short-fixed distance after release from an enclosure. We also investigated the association of cattle temperament with polymorphisms in bovine orthologs of risk genes for neuroticism, schizophrenia, autism spectrum disorders (ASD), and developmental delay disorders in humans. RESULTS: Variants with the strongest associations were located in the bovine orthologous region that is involved in several behavioural and cognitive disorders in humans. These variants were also partially validated in independent cattle cohorts. Genes in these regions (BARHL2, NDN, SNRPN, MAGEL2, ABCA12, KIFAP3, TOPAZ1, FZD3, UBE3A, and GABRA5) were enriched for the GO term neuron migration and were differentially expressed in brain and pituitary tissues in humans. Moreover, variants within 100 kb of ASD susceptibility genes were associated with cattle temperament and explained 6.5% of the total additive genetic variance in the largest cattle cohort. The ASD genes with the most significant associations were GABRB3 and CUL3. Using the same 100 kb window, a weak association was found with polymorphisms in schizophrenia risk genes and no association with polymorphisms in neuroticism and developmental delay disorders risk genes. CONCLUSIONS: Our analysis showed that genes identified in a meta-analysis of cattle temperament contribute to neuron development functions and are differentially expressed in human brain tissues. Furthermore, some ASD susceptibility genes are associated with cattle temperament. These findings provide evidence that genetic control of temperament might be shared between humans and cattle and highlight the potential for future analyses to leverage results between species.

Evaluation of the International Society for Animal Genetics bovine single nucleotide polymorphism parentage panel in South African Bonsmara and Drakensberger cattle.

A panel of 200 single nucleotide polymorphisms (SNPs) have been recommended by the International Society for Animal Genetics (ISAG) for use in parentage verification of cattle. While the SNPs included on the ISAG panel are segregating in European Bos taurus and Bos indicus breeds, their applicability in South African (SA) Sanga cattle has never been evaluated. This study, therefore, assessed the usefulness of the ISAG panel in SA Bonsmara (BON) and Drakensberger (DRB) cattle. Genotypes of 185 ISAG SNPs from 64 BON and 97 DRB sire-offspring pairs were available, all of which were validated with 119,375 SNPs. Of the 185 ISAG SNPs, 14 and 18 in the BON and DRB, respectively (9 in common to both breeds), were either monomorphic, exhibited at least one discordance between validated sire-offspring pairs, or had poor call rate or clustering issue. The mean minor allele frequency of the 185 ISAG SNPs was 0.331 in the BON and 0.359 in the DRB. The combined probability of parentage exclusion (PE) was the same (99.46%) for both breeds, while the probability of identity varied from 1.61 × 10-48 (BON) to 1.11 × 10-54 (DRB). Fifteen (23.4%) and 32 (33%) of the already validated sire-offspring pairs for the BON and DRB, respectively, were determined by the ISAG panel to be false-negatives based on a threshold of having at least two discordant SNPs. In comparison to sire discovery using the 119,375 SNPs, sire discovery using only the ISAG panel identified correctly 44 (out of 64 identified using the 119,375 SNPs) unique sire-offspring BON pairs and 62 (out of 97 identified using the 119,375 SNPs) unique sire-offspring DRB when all sires were masked. Five BON and three DRB offspring had > 1 sire nominated. This study demonstrated that the use of the ISAG panel may result in incorrect exclusions and multiple candidate sires for a given animal. Selection of more informative SNPs is, therefore, necessary in the pursuit of a low-cost and effective SNP panel for indigenous cattle breeds in SA.

Genome-wide association study of endo-parasite phenotypes using imputed whole-genome sequence data in dairy and beef cattle.

BACKGROUND: Quantitative genetic studies suggest the existence of variation at the genome level that affects the ability of cattle to resist to parasitic diseases. The objective of the current study was to identify regions of the bovine genome that are associated with resistance to endo-parasites. METHODS: Individual cattle records were available for Fasciola hepatica-damaged liver from 18 abattoirs. Deregressed estimated breeding values (EBV) for F. hepatica-damaged liver were generated for genotyped animals with a record for F. hepatica-damaged liver and for genotyped sires with a least one progeny record for F. hepatica-damaged liver; 3702 animals were available. In addition, individual cow records for antibody response to F. hepatica on 6388 genotyped dairy cows, antibody response to Ostertagia ostertagi on 8334 genotyped dairy cows and antibody response to Neospora caninum on 4597 genotyped dairy cows were adjusted for non-genetic effects. Genotypes were imputed to whole-sequence; after edits, 14,190,141 single nucleotide polymorphisms (SNPs) and 16,603,644 SNPs were available for cattle with deregressed EBV for F. hepatica-damaged liver and cows with an antibody response to a parasitic disease, respectively. Association analyses were undertaken using linear regression on one SNP at a time, in which a genomic relationship matrix accounted for the relationships between animals. RESULTS: Genomic regions for F. hepatica-damaged liver were located on Bos taurus autosomes (BTA) 1, 8, 11, 16, 17 and 18; each region included at least one SNP with a p value lower than 10-6. Five SNPs were identified as significant (q value < 0.05) for antibody response to N. caninum and were located on BTA21 or 25. For antibody response to F. hepatica and O. ostertagi, six and nine quantitative trait loci (QTL) regions that included at least one SNP with a p value lower than 10-6 were identified, respectively. Gene set enrichment analysis revealed a significant association between functional annotations related to the olfactory system and QTL that were suggestively associated with endo-parasite phenotypes. CONCLUSIONS: A number of novel genomic regions were suggestively associated with endo-parasite phenotypes across the bovine genome and two genomic regions on BTA21 and 25 were associated with antibody response to N. caninum.

Exploring a Possible Link between the Intestinal Microbiota and Feed Efficiency in Pigs.

Feed efficiency (FE) is critical in pig production for both economic and environmental reasons. As the intestinal microbiota plays an important role in energy harvest, it is likely to influence FE. Therefore, our aim was to characterize the intestinal microbiota of pigs ranked as low, medium, and high residual feed intake ([RFI] a metric for FE), where genetic, nutritional, and management effects were minimized, to explore a possible link between the intestinal microbiota and FE. Eighty-one pigs were ranked according to RFI between weaning and day 126 postweaning, and 32 were selected as the extremes in RFI (12 low, 10 medium, and 10 high). Intestinal microbiota diversity, composition, and predicted functionality were assessed by 16S rRNA gene sequencing. Although no differences in microbial diversity were found, some RFI-associated compositional differences were revealed, principally among members of Firmicutes, predominantly in feces at slaughter (albeit mainly for low-abundance taxa). In particular, microbes associated with a leaner and healthier host (e.g., Christensenellaceae, Oscillibacter, and Cellulosilyticum) were enriched in low RFI (more feed-efficient) pigs. Differences were also observed in the ileum of low RFI pigs; most notably, Nocardiaceae (Rhodococcus) were less abundant. Predictive functional analysis suggested improved metabolic capabilities in these animals, especially within the ileal microbiota. Higher ileal isobutyric acid concentrations were also found in low RFI pigs. Overall, the differences observed within the intestinal microbiota of low RFI pigs compared with that of their high RFI counterparts, albeit relatively subtle, suggest a possible link between the intestinal microbiota and FE in pigs.IMPORTANCE This study is one of the first to show that differences in intestinal microbiota composition, albeit subtle, may partly explain improved feed efficiency (FE) in low residual feed intake (RFI) pigs. One of the main findings is that, although microbial diversity did not differ among animals of varying FE, specific intestinal microbes could potentially be linked with porcine FE. However, as the factors impacting FE are still not fully understood, intestinal microbiota composition may not be a major factor determining differences in FE. Nonetheless, this work has provided a potential set of microbial biomarkers for FE in pigs. Although culturability could be a limiting factor and intervention studies are required, these taxa could potentially be targeted in the future to manipulate the intestinal microbiome so as to improve FE in pigs. If successful, this has the potential to reduce both production costs and the environmental impact of pig production.

Differentially Expressed Genes in Endometrium and Corpus Luteum of Holstein Cows Selected for High and Low Fertility Are Enriched for Sequence Variants Associated with Fertility.

Despite the importance of fertility in humans and livestock, there has been little success dissecting the genetic basis of fertility. Our hypothesis was that genes differentially expressed in the endometrium and corpus luteum on Day 13 of the estrous cycle between cows with either good or poor genetic merit for fertility would be enriched for genetic variants associated with fertility. We combined a unique genetic model of fertility (cattle that have been selected for high and low fertility and show substantial difference in fertility) with gene expression data from these cattle and genome-wide association study (GWAS) results in ∼20,000 cattle to identify quantitative trait loci (QTL) regions and sequence variants associated with genetic variation in fertility. Two hundred and forty-five QTL regions and 17 sequence variants associated primarily with prostaglandin F2alpha, steroidogenesis, mRNA processing, energy status, and immune-related processes were identified. Ninety-three of the QTL regions were validated by two independent GWAS, with signals for fertility detected primarily on chromosomes 18, 5, 7, 8, and 29. Plausible causative mutations were identified, including one missense variant significantly associated with fertility and predicted to affect the protein function of EIF4EBP3. The results of this study enhance our understanding of 1) the contribution of the endometrium and corpus luteum transcriptome to phenotypic fertility differences and 2) the genetic architecture of fertility in dairy cattle. Including these variants in predictions of genomic breeding values may improve the rate of genetic gain for this critical trait.

A genome-wide association study for genetic susceptibility to Mycobacterium bovis infection in dairy cattle identifies a susceptibility QTL on chromosome 23.

BACKGROUND: Bovine tuberculosis (bTB) infection in cattle is a significant economic concern in many countries, with annual costs to the UK and Irish governments of approximately €190 million and €63 million, respectively, for bTB control. The existence of host additive and non-additive genetic components to bTB susceptibility has been established. METHODS: Two approaches i.e. single-SNP (single nucleotide polymorphism) regression and a Bayesian method were applied to genome-wide association studies (GWAS) using high-density SNP genotypes (n = 597,144 SNPs) from 841 dairy artificial insemination (AI) sires. Deregressed estimated breeding values for bTB susceptibility were used as the quantitative dependent variable. Network analysis was performed using the quantitative trait loci (QTL) that were identified as significant in the single-SNP regression and Bayesian analyses separately. In addition, an identity-by-descent analysis was performed on a subset of the most prolific sires in the dataset that showed contrasting prevalences of bTB infection in daughters. RESULTS: A significant QTL region was identified on BTA23 (P value >1 × 10(-5), Bayes factor >10) across all analyses. Sires with the minor allele (minor allele frequency = 0.136) for this QTL on BTA23 had estimated breeding values that conferred a greater susceptibility to bTB infection than those that were homozygous for the major allele. Imputation of the regions that flank this QTL on BTA23 to full sequence indicated that the most significant associations were located within introns of the FKBP5 gene. CONCLUSIONS: A genomic region on BTA23 that is strongly associated with host susceptibility to bTB infection was identified. This region contained FKBP5, a gene involved in the TNFα/NFκ-B signalling pathway, which is a major biological pathway associated with immune response. Although there is no study that validates this region in the literature, our approach represents one of the most powerful studies for the analysis of bTB susceptibility to date.

Inter- and intra-reproducibility of genotypes from sheep technical replicates on Illumina and Affymetrix platforms.

BACKGROUND: Accurate genomic analyses are predicated upon access to accurate genotype input data. The objective of this study was to quantify the reproducibility of genotype data that are generated from the same genotype platform and from different genotyping platforms. METHODS: Genotypes based on 51,121 single nucleotide polymorphisms (SNPs) for 84 animals that were each genotyped on Illumina and Affymetrix platforms and for another 25 animals that were each genotyped twice on the same Illumina platform were compared. Genotypes based on 11,323 SNPs for an additional 21 animals that were genotyped on two different Illumina platforms by two different service providers were also compared. Reproducibility of the results was measured as the correlation between allele counts and as genotype and allele concordance rates. RESULTS: A mean within-animal correlation of 0.9996 was found between allele counts in the 25 duplicate samples that were genotyped on the same Illumina platform and varied from 0.9963 to 1.0000 per animal. The mean (minimum, maximum) genotype and allele concordance rates per animal between the 25 duplicate samples were equal to 0.9996 (0.9968, 1.0000) and 0.9993 (0.9937, 1.0000), respectively. The concordance rate between the two different Illumina platforms was also near 1. A mean within-animal correlation of 0.9738 was found between genotypes that were generated on the Illumina and Affymetrix platforms and varied from 0.9505 to 0.9812 per animal. The mean (minimum, maximum) within-animal genotype and allele concordance rates between the Illumina and Affymetrix platforms were equal to 0.9711 (0.9418, 0.9798) and 0.9845 (0.9695, 0.9889), respectively. The genotype concordance rate across all genotypes increased from 0.9711 to 0.9949 when the SNPs used were restricted to those with three high-resolution genotype clusters which represented 75.2% of the called genotypes. CONCLUSIONS AND IMPLICATIONS: Our results suggest that, regardless of the genotype platform or service provider, high genotype concordance rates are achieved especially if they are restricted to high-quality extracted DNA and SNPs that result in high-quality genotypes.

Offspring subcutaneous adipose markers are sensitive to the timing of maternal gestational weight gain.

BACKGROUND: Excessive maternal weight gain during pregnancy impacts on offspring health. This study focused on the timing of maternal gestational weight gain, using a porcine model with mothers of normal pre-pregnancy weight. METHODS: Trial design ensured the trajectory of maternal gestational weight gain differed across treatments in early, mid and late gestation. Diet composition did not differ. On day 25 gestation, sows were assigned to one of five treatments: Control sows received a standard gestation diet of 2.3 kg/day (30 MJ DE/day) from early to late gestation (day 25-110 gestation). E sows received 4.6 kg food/day in early gestation (day 25-50 gestation). M sows doubled their food intake in mid gestation (day 50-80 gestation). EM sows doubled their food intake during both early and mid gestation (day 25-80 gestation). L sows consumed 3.5 kg food/day in late gestation (day 80-110 gestation). Offspring body weight and food intake levels were measured from birth to adolescence. Markers of lipid metabolism, hypertrophy and inflammation were investigated in subcutaneous adipose tissue of adolescent offspring. RESULTS: The trajectory of gestational weight gain differed across treatments. However total gestational weight gain did not differ except for EM sows who were the heaviest and fattest mothers at parturition. Offspring birth weight did not differ across treatments. Subcutaneous adipose tissue from EM offspring differed significantly from controls, with elevated mRNA levels of lipogenic (CD36, ACACB and LPL), nutrient transporters (FABP4 and GLUT4), lipolysis (HSL and ATGL), adipocyte size (MEST) and inflammation (PAI-1) indicators. The subcutaneous adipose depot from L offspring exhibited elevated levels of CD36, ACACB, LPL, GLUT4 and FABP4 mRNA transcripts compared to control offspring. CONCLUSIONS: Increasing gestational weight gain in early gestation had the greatest impact on offspring postnatal growth rate. Increasing maternal food allowance in late gestation appeared to shift the offspring adipocyte focus towards accumulation of fat. Mothers who gained the most weight during gestation (EM mothers) gave birth to offspring whose subcutaneous adipose tissue, at adolescence, appeared hyperactive compared to controls. This study concluded that mothers, who gained more than the recommended weight gain in mid and late gestation, put their offspring adipose tissue at risk of dysfunction.