Investigation of ancestral alleles in the Bovinae subfamily.

BACKGROUND: In evolutionary theory, divergence and speciation can arise from long periods of reproductive isolation, genetic mutation, selection and environmental adaptation. After divergence, alleles can either persist in their initial state (ancestral allele - AA), co-exist or be replaced by a mutated state (derived alleles -DA). In this study, we aligned whole genome sequences of individuals from the Bovinae subfamily to the cattle reference genome (ARS.UCD-1.2) for defining ancestral alleles necessary for selection signatures study. RESULTS: Accommodating independent divergent of each lineage from the initial ancestral state, AA were defined based on fixed alleles on at least two groups of yak, bison and gayal-gaur-banteng resulting in ~ 32.4 million variants. Using non-overlapping scanning windows of 10 Kb, we counted the AA observed within taurine and zebu cattle. We focused on the extreme points, regions with top 0. 1% (high count) and regions without any occurrence of AA (null count). High count regions preserved gene functions from ancestral states that are still beneficial in the current condition, while null counts regions were linked to mutated ones. For both cattle, high count regions were associated with basal lipid metabolism, essential for survival of various environmental pressures. Mutated regions were associated to productive traits in taurine, i.e. higher metabolism, cell development and behaviors and in immune response domain for zebu. CONCLUSIONS: Our findings suggest that retaining and losing AA in some regions are varied and made it species-specific with possibility of overlapping as it depends on the selective pressure they had to experience.

Assessing Bos taurus introgression in the UOA Bos indicus assembly.

BACKGROUND: Reference genomes are essential in the analysis of genomic data. As the cost of sequencing decreases, multiple reference genomes are being produced within species to alleviate problems such as low mapping accuracy and reference allele bias in variant calling that can be associated with the alignment of divergent samples to a single reference individual. The latest reference sequence adopted by the scientific community for the analysis of cattle data is ARS_UCD1.2, built from the DNA of a Hereford cow (Bos taurus taurus-B. taurus). A complementary genome assembly, UOA_Brahman_1, was recently built to represent the other cattle subspecies (Bos taurus indicus-B. indicus) from a Brahman cow haplotype to further support analysis of B. indicus data. In this study, we aligned the sequence data of 15 B. taurus and B. indicus breeds to each of these references. RESULTS: The alignment of B. taurus individuals against UOA_Brahman_1 detected up to five million more single-nucleotide variants (SNVs) compared to that against ARS_UCD1.2. Similarly, the alignment of B. indicus individuals against ARS_UCD1.2 resulted in one and a half million more SNVs than that against UOA_Brahman_1. The number of SNVs with nearly fixed alternative alleles also increased in the alignments with cross-subspecies. Interestingly, the alignment of B. taurus cattle against UOA_Brahman_1 revealed regions with a smaller than expected number of counts of SNVs with nearly fixed alternative alleles. Since B. taurus introgression represents on average 10% of the genome of Brahman cattle, we suggest that these regions comprise taurine DNA as opposed to indicine DNA in the UOA_Brahman_1 reference genome. Principal component and admixture analyses using genotypes inferred from this region support these taurine-introgressed loci. Overall, the flagged taurine segments represent 13.7% of the UOA_Brahman_1 assembly. The genes located within these segments were previously reported to be under positive selection in Brahman cattle, and include functional candidate genes implicated in feed efficiency, development and immunity. CONCLUSIONS: We report a list of taurine segments that are in the UOA_Brahman_1 assembly, which will be useful for the interpretation of interesting genomic features (e.g., signatures of selection, runs of homozygosity, increased mutation rate, etc.) that could appear in future re-sequencing analysis of indicine cattle.

Variants at the ASIP locus contribute to coat color darkening in Nellore cattle.

BACKGROUND: Nellore cattle (Bos indicus) are well-known for their adaptation to warm and humid environments. Hair length and coat color may impact heat tolerance. The Nellore breed has been strongly selected for white coat, but bulls generally exhibit darker hair ranging from light grey to black on the head, neck, hump, and knees. Given the potential contribution of coat color variation to the adaptation of cattle populations to tropical and sub-tropical environments, our aim was to map positional and functional candidate genetic variants associated with darkness of hair coat (DHC) in Nellore bulls. RESULTS: We performed a genome-wide association study (GWAS) for DHC using data from 432 Nellore bulls that were genotyped for more than 777 k single nucleotide polymorphism (SNP) markers. A single major association signal was detected in the vicinity of the agouti signaling protein gene (ASIP). The analysis of whole-genome sequence (WGS) data from 21 bulls revealed functional variants that are associated with DHC, including a structural rearrangement involving ASIP (ASIP-SV1). We further characterized this structural variant using Oxford Nanopore sequencing data from 13 Australian Brahman heifers, which share ancestry with Nellore cattle; we found that this variant originates from a 1155-bp deletion followed by an insertion of a transposable element of more than 150 bp that may impact the recruitment of ASIP non-coding exons. CONCLUSIONS: Our results indicate that the variant ASIP sequence causes darker coat pigmentation on specific parts of the body, most likely through a decreased expression of ASIP and consequently an increased production of eumelanin.

Genomic predictions combining SNP markers and copy number variations in Nellore cattle.

BACKGROUND: Due to the advancement in high throughput technology, single nucleotide polymorphism (SNP) is routinely being incorporated along with phenotypic information into genetic evaluation. However, this approach often cannot achieve high accuracy for some complex traits. It is possible that SNP markers are not sufficient to predict these traits due to the missing heritability caused by other genetic variations such as microsatellite and copy number variation (CNV), which have been shown to affect disease and complex traits in humans and other species. RESULTS: In this study, CNVs were included in a SNP based genomic selection framework. A Nellore cattle dataset consisting of 2230 animals genotyped on BovineHD SNP array was used, and 9 weight and carcass traits were analyzed. A total of six models were implemented and compared based on their prediction accuracy. For comparison, three models including only SNPs were implemented: 1) BayesA model, 2) Bayesian mixture model (BayesB), and 3) a GBLUP model without polygenic effects. The other three models incorporating both SNP and CNV included 4) a Bayesian model similar to BayesA (BayesA+CNV), 5) a Bayesian mixture model (BayesB+CNV), and 6) GBLUP with CNVs modeled as a covariable (GBLUP+CNV). Prediction accuracies were assessed based on Pearson's correlation between de-regressed EBVs (dEBVs) and direct genomic values (DGVs) in the validation dataset. For BayesA, BayesB and GBLUP, accuracy ranged from 0.12 to 0.62 across the nine traits. A minimal increase in prediction accuracy for some traits was noticed when including CNVs in the model (BayesA+CNV, BayesB+CNV, GBLUP+CNV). CONCLUSIONS: This study presents the first genomic prediction study integrating CNVs and SNPs in livestock. Combining CNV and SNP marker information proved to be beneficial for genomic prediction of some traits in Nellore cattle.

Misidentification of runs of homozygosity islands in cattle caused by interference with copy number variation or large intermarker distances.

BACKGROUND: Runs of homozygosity (ROH) islands are stretches of homozygous sequence in the genome of a large proportion of individuals in a population. Algorithms for the detection of ROH depend on the similarity of haplotypes. Coverage gaps and copy number variants (CNV) may result in incorrect identification of such similarity, leading to the detection of ROH islands where none exists. Misidentified hemizygous regions will also appear as homozygous based on sequence variation alone. Our aim was to identify ROH islands influenced by marker coverage gaps or CNV, using Illumina BovineHD BeadChip (777 K) single nucleotide polymorphism (SNP) data for Austrian Brown Swiss, Tyrol Grey and Pinzgauer cattle. METHODS: ROH were detected using clustering, and ROH islands were determined from population inbreeding levels for each marker. CNV were detected using a multivariate copy number analysis method and a hidden Markov model. SNP coverage gaps were defined as genomic regions with intermarker distances on average longer than 9.24 kb. ROH islands that overlapped CNV regions (CNVR) or SNP coverage gaps were considered as potential artefacts. Permutation tests were used to determine if overlaps between CNVR with copy losses and ROH islands were due to chance. Diversity of the haplotypes in the ROH islands was assessed by haplotype analyses. RESULTS: In Brown Swiss, Tyrol Grey and Pinzgauer, we identified 13, 22, and 24 ROH islands covering 26.6, 389.0 and 35.8 Mb, respectively, and we detected 30, 50 and 71 CNVR derived from CNV by using both algorithms, respectively. Overlaps between ROH islands, CNVR or coverage gaps occurred for 7, 14 and 16 ROH islands, respectively. About 37, 44 and 52% of the ROH islands coverage in Brown Swiss, Tyrol Grey and Pinzgauer, respectively, were affected by copy loss. Intersections between ROH islands and CNVR were small, but significantly larger compared to ROH islands at random locations across the genome, implying an association between ROH islands and CNVR. Haplotype diversity for reliable ROH islands was lower than for ROH islands that intersected with copy loss CNVR. CONCLUSIONS: Our findings show that a significant proportion of the ROH islands in the bovine genome are artefacts due to CNV or SNP coverage gaps.

GHap: an R package for genome-wide haplotyping.

UNLABELLED: The GHap R package was designed to call haplotypes from phased marker data. Given user-defined haplotype blocks (HapBlock), the package identifies the different haplotype alleles (HapAllele) present in the data and scores sample haplotype allele genotypes (HapGenotype) based on HapAllele dose (i.e. 0, 1 or 2 copies). The output is not only useful for analyses that can handle multi-allelic markers, but is also conveniently formatted for existing pipelines intended for bi-allelic markers. AVAILABILITY AND IMPLEMENTATION: https://cran.r-project.org/package=GHap CONTACT: ytutsunomiya@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum.

A genome-wide association study (GWAS) could unravel the complexity of the cell-mediated immunity (CMI) to canine leishmaniasis (CanL). Therefore, we scanned 110,165 single-nucleotide polymorphisms (SNPs), aiming to identify chromosomal regions associated with the leishmanin skin test (LST), lymphocyte proliferation assay (LPA), and cytokine responses to further understand the role played by CMI in the outcome of natural Leishmania infantum infection in 189 dogs. Based on LST and LPA, four CMI profiles were identified (LST-/LPA-, LST+/LPA-, LST-/LPA+, and LST+/LPA+), which were not associated with subclinically infected or diseased dogs. LST+/LPA+ dogs showed increased interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) levels and mild parasitism in the lymph nodes, whereas LST-/LPA+ dogs, in spite of increased IFN-γ, also showed increased interleukin-10 (IL-10) and transforming growth factor ß (TGF-ß) levels and the highest parasite load in lymph nodes. Low T cell proliferation under low parasite load suggested that L. infantum was not able to induce effective CMI in the early stage of infection. Altogether, genetic markers explained 87%, 16%, 15%, 11%, 0%, and 0% of phenotypic variance in TNF-α, TGF-ß, LST, IL-10, IFN-γ, and LPA, respectively. GWAS showed that regions associated with TNF-α include the following genes: IL12RB1, JAK3, CCRL2, CCR2, CCR3, and CXCR6, involved in cytokine and chemokine signaling; regions associated with LST, including COMMD5 and SHARPIN, involved in regulation of NF-κB signaling; and regions associated with IL-10, including LTBP1 and RASGRP3, involved in T regulatory lymphocytes differentiation. These findings pinpoint chromosomic regions related to the cell-mediated response that potentially affect the clinical complexity and the parasite replication in canine L. infantum infection.

Revealing misassembled segments in the bovine reference genome by high resolution linkage disequilibrium scan.

BACKGROUND: Misassembly signatures, created by shuffling the order of sequences while assembling a genome, can be detected by the unexpected behavior of marker linkage disequilibrium (LD) decay. We developed a heuristic process to identify misassembly signatures, applied it to the bovine reference genome assembly (UMDv3.1) and presented the consequences of misassemblies in two case studies. RESULTS: We identified 2,906 single nucleotide polymorphism (SNP) markers presenting unexpected LD decay behavior in 626 putative misassembled contigs, which comprised less than 1 % of the whole genome. Although this represents a small fraction of the reference sequence, these poorly assembled segments can lead to severe implications to local genome context. For instance, we showed that one of the misassembled regions mapped to the POLL locus, which affected the annotation of positional candidate genes in a GWAS case study for polledness in Nellore (Bos indicus beef cattle). Additionally, we found that poorly performing markers in imputation mapped to putative misassembled regions, and that correction of marker positions based on LD was capable to recover imputation accuracy. CONCLUSIONS: This heuristic approach can be useful to cross validate reference assemblies and to filter out markers located at low confidence genomic regions before conducting downstream analyses.

Genome-wide CNV analysis reveals variants associated with growth traits in Bos indicus.

BACKGROUND: Apart from single nucleotide polymorphism (SNP), copy number variation (CNV) is another important type of genetic variation, which may affect growth traits and play key roles for the production of beef cattle. To date, no genome-wide association study (GWAS) for CNV and body traits in beef cattle has been reported, so the present study aimed to investigate this type of association in one of the most important cattle subspecies: Bos indicus (Nellore breed). RESULTS: We have used intensity data from over 700,000 SNP probes across the bovine genome to detect common CNVs in a sample of 2230 Nellore cattle, and performed GWAS between the detected CNVs and nine growth traits. After filtering for frequency and length, a total of 231 CNVs ranging from 894 bp to 4,855,088 bp were kept and tested as predictors for each growth trait using linear regression analysis with principal components correction. There were 49 significant associations identified among 17 CNVs and seven body traits after false discovery rate correction (P < 0.05). Among the 17 CNVs, three were significant or marginally significant for all the traits. We have compared the locations of associated CNVs with quantitative trait locus and the RefGene database, and found two sets of 9 CNVs overlapping with either known QTLs or genes, respectively. The gene overlapping with CNV100, KCNJ12, is a functional candidate for muscle development and plays critical roles in muscling traits. CONCLUSION: This study presents the first CNV-based GWAS of growth traits using high density SNP microarray data in cattle. We detected 17 CNVs significantly associated with seven growth traits and one of them (CNV100) may be involved in growth traits through KCNJ12.

Low levels of taurine introgression in the current Brazilian Nelore and Gir indicine cattle populations.

BACKGROUND: Nelore and Gir are the two most important indicine cattle breeds for production of beef and milk in Brazil. Historical records state that these breeds were introduced in Brazil from the Indian subcontinent, crossed to local taurine cattle in order to quickly increase the population size, and then backcrossed to the original breeds to recover indicine adaptive and productive traits. Previous investigations based on sparse DNA markers detected taurine admixture in these breeds. High-density genome-wide analyses can provide high-resolution information on the genetic composition of current Nelore and Gir populations, estimate more precisely the levels and nature of taurine introgression, and shed light on their history and the strategies that were used to expand these breeds. RESULTS: We used the high-density Illumina BovineHD BeadChip with more than 777 K single nucleotide polymorphisms (SNPs) that were reduced to 697 115 after quality control filtering to investigate the structure of Nelore and Gir populations and seven other worldwide populations for comparison. Multidimensional scaling and model-based ancestry estimation clearly separated the indicine, European taurine and African taurine ancestries. The average level of taurine introgression in the autosomal genome of Nelore and Gir breeds was less than 1% but was 9% for the Brahman breed. Analyses based on the mitochondrial SNPs present in the Illumina BovineHD BeadChip did not clearly differentiate taurine and indicine haplotype groupings. CONCLUSIONS: The low level of taurine ancestry observed for both Nelore and Gir breeds confirms the historical records of crossbreeding and supports a strong directional selection against taurine haplotypes via backcrossing. Random sampling in production herds across the country and subsequent genotyping would be useful for a more complete view of the admixture levels in the commercial Nelore and Gir populations.

Genome-wide association analysis of feed intake and residual feed intake in Nellore cattle.

BACKGROUND: Feed intake plays an important economic role in beef cattle, and is related with feed efficiency, weight gain and carcass traits. However, the phenotypes collected for dry matter intake and feed efficiency are scarce when compared with other measures such as weight gain and carcass traits. The use of genomic information can improve the power of inference of studies on these measures, identifying genomic regions that affect these phenotypes. This work performed the genome-wide association study (GWAS) for dry matter intake (DMI) and residual feed intake (RFI) of 720 Nellore cattle (Bos taurus indicus). RESULTS: In general, no genomic region extremely associated with both phenotypic traits was observed, as expected for the variables that have their regulation controlled by many genes. Three SNPs surpassed the threshold for the Bonferroni multiple test for DMI and two SNPs for RFI. These markers are located on chromosomes 4, 8, 14 and 21 in regions near genes regulating appetite and ion transport and close to important QTL as previously reported to RFI and DMI, thus corroborating the literature that points these two processes as important in the physiological regulation of intake and feed efficiency. CONCLUSIONS: This study showed the first GWAS of DMI to identify genomic regions associated with feed intake and efficiency in Nellore cattle. Some genes and QTLs previously described for DMI and RFI, in other subspecies (Bos taurus taurus), that influences these phenotypes are confirmed in this study.

Accuracy of genotype imputation in Nelore cattle.

BACKGROUND: Genotype imputation from low-density (LD) to high-density single nucleotide polymorphism (SNP) chips is an important step before applying genomic selection, since denser chips tend to provide more reliable genomic predictions. Imputation methods rely partially on linkage disequilibrium between markers to infer unobserved genotypes. Bos indicus cattle (e.g. Nelore breed) are characterized, in general, by lower levels of linkage disequilibrium between genetic markers at short distances, compared to taurine breeds. Thus, it is important to evaluate the accuracy of imputation to better define which imputation method and chip are most appropriate for genomic applications in indicine breeds. METHODS: Accuracy of genotype imputation in Nelore cattle was evaluated using different LD chips, imputation software and sets of animals. Twelve commercial and customized LD chips with densities ranging from 7 K to 75 K were tested. Customized LD chips were virtually designed taking into account minor allele frequency, linkage disequilibrium and distance between markers. Software programs FImpute and BEAGLE were applied to impute genotypes. From 995 bulls and 1247 cows that were genotyped with the Illumina® BovineHD chip (HD), 793 sires composed the reference set, and the remaining 202 younger sires and all the cows composed two separate validation sets for which genotypes were masked except for the SNPs of the LD chip that were to be tested. RESULTS: Imputation accuracy increased with the SNP density of the LD chip. However, the gain in accuracy with LD chips with more than 15 K SNPs was relatively small because accuracy was already high at this density. Commercial and customized LD chips with equivalent densities presented similar results. FImpute outperformed BEAGLE for all LD chips and validation sets. Regardless of the imputation software used, accuracy tended to increase as the relatedness between imputed and reference animals increased, especially for the 7 K chip. CONCLUSIONS: If the Illumina® BovineHD is considered as the target chip for genomic applications in the Nelore breed, cost-effectiveness can be improved by genotyping part of the animals with a chip containing around 15 K useful SNPs and imputing their high-density missing genotypes with FImpute.

Assessing signatures of selection through variation in linkage disequilibrium between taurine and indicine cattle.

BACKGROUND: Signatures of selection are regions in the genome that have been preferentially increased in frequency and fixed in a population because of their functional importance in specific processes. These regions can be detected because of their lower genetic variability and specific regional linkage disequilibrium (LD) patterns. METHODS: By comparing the differences in regional LD variation between dairy and beef cattle types, and between indicine and taurine subspecies, we aim at finding signatures of selection for production and adaptation in cattle breeds. The VarLD method was applied to compare the LD variation in the autosomal genome between breeds, including Angus and Brown Swiss, representing taurine breeds, and Nelore and Gir, representing indicine breeds. Genomic regions containing the top 0.01 and 0.1 percentile of signals were characterized using the UMD3.1 Bos taurus genome assembly to identify genes in those regions and compared with previously reported selection signatures and regions with copy number variation. RESULTS: For all comparisons, the top 0.01 and 0.1 percentile included 26 and 165 signals and 17 and 125 genes, respectively, including TECRL, BT.23182 or FPPS, CAST, MYOM1, UVRAG and DNAJA1. CONCLUSIONS: The VarLD method is a powerful tool to identify differences in linkage disequilibrium between cattle populations and putative signatures of selection with potential adaptive and productive importance.

Accuracy of genomic predictions in Bos indicus (Nellore) cattle.

BACKGROUND: Nellore cattle play an important role in beef production in tropical systems and there is great interest in determining if genomic selection can contribute to accelerate genetic improvement of production and fertility in this breed. We present the first results of the implementation of genomic prediction in a Bos indicus (Nellore) population. METHODS: Influential bulls were genotyped with the Illumina Bovine HD chip in order to assess genomic predictive ability for weight and carcass traits, gestation length, scrotal circumference and two selection indices. 685 samples and 320 238 single nucleotide polymorphisms (SNPs) were used in the analyses. A forward-prediction scheme was adopted to predict the genomic breeding values (DGV). In the training step, the estimated breeding values (EBV) of bulls were deregressed (dEBV) and used as pseudo-phenotypes to estimate marker effects using four methods: genomic BLUP with or without a residual polygenic effect (GBLUP20 and GBLUP0, respectively), a mixture model (Bayes C) and Bayesian LASSO (BLASSO). Empirical accuracies of the resulting genomic predictions were assessed based on the correlation between DGV and dEBV for the testing group. RESULTS: Accuracies of genomic predictions ranged from 0.17 (navel at weaning) to 0.74 (finishing precocity). Across traits, Bayesian regression models (Bayes C and BLASSO) were more accurate than GBLUP. The average empirical accuracies were 0.39 (GBLUP0), 0.40 (GBLUP20) and 0.44 (Bayes C and BLASSO). Bayes C and BLASSO tended to produce deflated predictions (i.e. slope of the regression of dEBV on DGV greater than 1). Further analyses suggested that higher-than-expected accuracies were observed for traits for which EBV means differed significantly between two breeding subgroups that were identified in a principal component analysis based on genomic relationships. CONCLUSIONS: Bayesian regression models are of interest for future applications of genomic selection in this population, but further improvements are needed to reduce deflation of their predictions. Recurrent updates of the training population would be required to enable accurate prediction of the genetic merit of young animals. The technical feasibility of applying genomic prediction in a Bos indicus (Nellore) population was demonstrated. Further research is needed to permit cost-effective selection decisions using genomic information.

Genomic divergence of zebu and taurine cattle identified through high-density SNP genotyping.

BACKGROUND: Natural selection has molded evolution across all taxa. At an arguable date of around 330,000 years ago there were already at least two different types of cattle that became ancestors of nearly all modern cattle, the Bos taurus taurus more adapted to temperate climates and the tropically adapted Bos taurus indicus. After domestication, human selection exponentially intensified these differences. To better understand the genetic differences between these subspecies and detect genomic regions potentially under divergent selection, animals from the International Bovine HapMap Experiment were genotyped for over 770,000 SNP across the genome and compared using smoothed F(ST). The taurine sample was represented by ten breeds and the contrasting zebu cohort by three breeds. RESULTS: Each cattle group evidenced similar numbers of polymorphic markers well distributed across the genome. Principal components analyses and unsupervised clustering confirmed the well-characterized main division of domestic cattle. The top 1% smoothed F(ST), potentially associated to positive selection, contained 48 genomic regions across 17 chromosomes. Nearly half of the top F(ST) signals (n = 22) were previously detected using a lower density SNP assay. Amongst the strongest signals were the BTA7:~50 Mb and BTA14:~25 Mb; both regions harboring candidate genes and different patterns of linkage disequilibrium that potentially represent intrinsic differences between cattle types. The bottom 1% of the smoothed F(ST) values, potentially associated to balancing selection, included 24 regions across 13 chromosomes. These regions often overlap with copy number variants, including the highly variable region at BTA23:~24 Mb that harbors a large number of MHC genes. Under these regions, 318 unique Ensembl genes are annotated with a significant overrepresentation of immune related pathways. CONCLUSIONS: Genomic regions that are potentially linked to purifying or balancing selection processes in domestic cattle were identified. These regions are of particular interest to understand the natural and human selective pressures to which these subspecies were exposed to and how the genetic background of these populations evolved in response to environmental challenges and human manipulation.

Genome-wide association study for birth weight in Nellore cattle points to previously described orthologous genes affecting human and bovine height.

BACKGROUND: Birth weight (BW) is an economically important trait in beef cattle, and is associated with growth- and stature-related traits and calving difficulty. One region of the cattle genome, located on Bos primigenius taurus chromosome 14 (BTA14), has been previously shown to be associated with stature by multiple independent studies, and contains orthologous genes affecting human height. A genome-wide association study (GWAS) for BW in Brazilian Nellore cattle (Bos primigenius indicus) was performed using estimated breeding values (EBVs) of 654 progeny-tested bulls genotyped for over 777,000 single nucleotide polymorphisms (SNPs). RESULTS: The most significant SNP (rs133012258, PGC = 1.34 × 10-9), located at BTA14:25376827, explained 4.62% of the variance in BW EBVs. The surrounding 1 Mb region presented high identity with human, pig and mouse autosomes 8, 4 and 4, respectively, and contains the orthologous height genes PLAG1, CHCHD7, MOS, RPS20, LYN, RDHE2 (SDR16C5) and PENK. The region also overlapped 28 quantitative trait loci (QTLs) previously reported in literature by linkage mapping studies in cattle, including QTLs for birth weight, mature height, carcass weight, stature, pre-weaning average daily gain, calving ease, and gestation length. CONCLUSIONS: This study presents the first GWAS applying a high-density SNP panel to identify putative chromosome regions affecting birth weight in Nellore cattle. These results suggest that the QTLs on BTA14 associated with body size in taurine cattle (Bos primigenius taurus) also affect birth weight and size in zebu cattle (Bos primigenius indicus).

Favored single nucleotide variants identified using whole genome Re-sequencing of Austrian and Chinese cattle breeds.

Cattle have been essential for the development of human civilization since their first domestication few thousand years ago. Since then, they have spread across vast geographic areas following human activities. Throughout generations, the cattle genome has been shaped with detectable signals induced by various evolutionary processes, such as natural and human selection processes and demographic events. Identifying such signals, called selection signatures, is one of the primary goals of population genetics. Previous studies used various selection signature methods and normalized the outputs score using specific windows, in kbp or based on the number of SNPs, to identify the candidate regions. The recent method of iSAFE claimed for high accuracy in pinpointing the candidate SNPs. In this study, we analyzed whole-genome resequencing (WGS) data of ten individuals from Austrian Fleckvieh (Bos taurus) and fifty individuals from 14 Chinese indigenous breeds (Bos taurus, Bos taurus indicus, and admixed). Individual WGS reads were aligned to the cattle reference genome of ARS. UCD1.2 and subsequently undergone single nucleotide variants (SNVs) calling pipeline using GATK. Using these SNVs, we examined the population structure using principal component and admixture analysis. Then we refined selection signature candidates using the iSAFE program and compared it with the classical iHS approach. Additionally, we run Fst population differentiation from these two cattle groups. We found gradual changes of taurine in north China to admixed and indicine to the south. Based on the population structure and the number of individuals, we grouped samples to Fleckvieh, three Chinese taurines (Kazakh, Mongolian, Yanbian), admixed individuals (CHBI_Med), indicine individuals (CHBI_Low), and a combination of admixed and indicine (CHBI) for performing iSAFE and iHS tests. There were more significant SNVs identified using iSAFE than the iHS for the candidate of positive selection and more detectable signals in taurine than in indicine individuals. However, combining admixed and indicine individuals decreased the iSAFE signals. From both within-population tests, significant SNVs are linked to the olfactory receptors, production, reproduction, and temperament traits in taurine cattle, while heat and parasites tolerance in the admixed individuals. Fst test suggests similar patterns of population differentiation between Fleckvieh and three Chinese taurine breeds against CHBI. Nevertheless, there are genes shared only among the Chinese taurine, such as PAX5, affecting coat color, which might drive the differences between these yellowish coated breeds, and those in the greater Far East region.

Chromosomal segments may explain the antibody response cooperation for canine leishmaniasis pathogenesis.

Visceral leishmaniasis (VL) is marked by hyperactivation of a humoral response secreting high quantity of immunoglobulins (Igs) that are inaccessible to intracellular parasites. Here we investigated the contributions of the antibody response to the canine leishmaniasis pathogenesis. Using correlation and genome-wide association analysis, we investigated the relationship of anti-Leishmania infantum immunoglobulin classes levels with parasite burden, clinical response, renal/hepatic biochemical, and oxidative stress markers in dogs from endemic areas of VL. Immunoglobulin G (IgG) and IgA were positively correlated with parasite burden on lymph node and blood. Increased IgG, IgA and IgE levels were associated with severe canine leishmaniasis (CanL) whereas IgM was elevated in uninfected exposed dogs. Correlations of IgM, IgG and IgA with creatinine, urea, AST and ALT levels in the serum were suggested an involvement of those Igs with renal and hepatic changes. The correlogram of oxidative radicals and antioxidants revealed a likely relationship of IgM, IgG and IgA with oxidative stress and lipid peroxidation in the blood, suggested as mechanisms mediating tissue damage and CanL worsening. The gene mapping on chromosomal segments associated with the quantitative variation of immunoglobulin classes identified genetic signatures involved with reactive oxygen species generation, phagolysosome maturation and rupture, free iron availability, Th1/Th2 differenciation and, immunoglobulin clearance. The findings demonstrated the roles of the antibody response as resistance or susceptibility markers and mediators of CanL pathogenesis. In addition we pinpointed candidate genes as potential targets for the therapy against the damage caused by exacerbated antibody response and parasitism in VL.

Timing and Extent of Inbreeding in African Goats.

Genetic characterization of African goats is one of the current priorities in the improvement of goats in the continent. This study contributes to the characterization effort by determining the levels and number of generations to common ancestors ("age") associated with inbreeding in African goat breeds and identifies regions that contain copy number variation mistyped as being homozygous. Illumina 50k single nucleotide polymorphism genotype data for 608 goats from 31 breeds were used to compute the level and age of inbreeding at both local (marker) and global levels (FG) using a model-based approach based on a hidden Markov model. Runs of homozygosity (ROH) segments detected using the Viterbi algorithm led to ROH-based inbreeding coefficients for all ROH (FROH) and for ROH longer than 2 Mb (FROH > 2Mb). Some of the genomic regions identified as having ROH are likely to be hemizygous regions (copy number deletions) mistyped as homozygous regions. Although the proportion of these miscalled ROH is small and does not substantially affect estimates of levels of inbreeding for individual animals, the inbreeding metrics were adjusted by removing these regions from the ROH. All the inbreeding metrics varied widely across breeds, with overall means of 0.0408, 0.0370, and 0.0691 and medians of 0.0125, 0.0098, and 0.0366 for FROH, FROH > 2Mb, and FG, respectively. Several breeds (including Menabe and Sofia from Madagascar) had high proportions of recent inbreeding, while Small East African, Ethiopian, and most of the West African breeds (including West African Dwarf) had more ancient inbreeding.

Canine leishmaniasis: Genome-wide analysis and antibody response to Lutzomyia longipalpis saliva.

The anti-inflammatory properties of sand fly saliva favor the establishment of the Leishmania infantum infection. In contrast, an antibody response against Lutzomyia longipalpis saliva is often associated with a protective cell-mediated response against canine visceral leishmaniasis. Genetic studies may demonstrate to what extent the ability to secrete anti-saliva antibodies depends on genetic or environmental factors. However, the genetic basis of canine antibody response against sand fly saliva has not been assessed. The aim of this study was to identify chromosomal regions associated with the anti-Lu. longipalpis salivary IgG response in 189 dogs resident in endemic areas in order to provide information for prophylactic strategies. Dogs were classified into five groups based on serological and parasitological diagnosis and clinical evaluation. Anti-salivary gland homogenate (SGH) IgG levels were assessed by Enzyme-Linked Immunosorbent Assay (ELISA). Genomic DNA was isolated from blood samples and genotyped using a SNP chip with 173,662 single nucleotide polymorphism (SNP) markers. The following linear regression model was fitted: IgG level = mean + origin + sex + age + use of a repellent collar, and the residuals were assumed as pseudo-phenotypes for the association test between phenotypes and genotypes (GWA). A component of variance model that takes into account polygenic and sample structure effects (EMMAX) was employed for GWA. Phenotypic findings indicated that anti-SGH IgG levels remained higher in exposed and subclinically infected dogs than in severely diseased dogs even in regression model residuals. Five associated markers were identified on chromosomes 2, 20 and 31. The mapped genes included CD180 (RP105) and MITF related to the rapid activation of B lymphocytes and differentiation into antibody-secreting plasma cells. The findings pointed to chromosomal segments useful for functional confirmation studies and a search for adjuvant molecules of the anti-saliva response.