Feet and legs malformation in Nellore cattle: genetic analysis and prioritization of GWAS results.

Beef cattle affected by feet and legs malformations (FLM) cannot perform their productive and reproductive functions satisfactorily, resulting in significant economic losses. Accelerated weight gain in young animals due to increased fat deposition can lead to ligaments, tendon and joint strain and promote gene expression patterns that lead to changes in the normal architecture of the feet and legs. The possible correlated response in the FLM due to yearling weight (YW) selection suggest that this second trait could be used as an indirect selection criterion. Therefore, FLM breeding values and the genetic correlation between FLM and yearling weight (YW) were estimated for 295,031 Nellore animals by fitting a linear-threshold model in a Bayesian approach. A genome-wide association study was performed to identify genomic windows and positional candidate genes associated with FLM. The effects of single nucleotide polymorphisms (SNPs) on FLM phenotypes (affected or unaffected) were estimated using the weighted single-step genomic BLUP method, based on genotypes of 12,537 animals for 461,057 SNPs. Twelve non-overlapping windows of 20 adjacent SNPs explaining more than 1% of the additive genetic variance were selected for candidate gene annotation. Functional and gene prioritization analysis of candidate genes identified six genes (ATG7, EXT1, ITGA1, PPARD, SCUBE3, and SHOX) that may play a role in FLM expression due to their known role in skeletal muscle development, aberrant bone growth, lipid metabolism, intramuscular fat deposition and skeletogenesis. Identifying genes linked to foot and leg malformations enables selective breeding for healthier herds by reducing the occurrence of these conditions. Genetic markers can be used to develop tests that identify carriers of these mutations, assisting breeders in making informed breeding decisions to minimize the incidence of malformations in future generations, resulting in greater productivity and animal welfare.

Testicular hypoplasia in Nellore Cattle: Genetic analysis and functional analysis of genome-wide association study results.

Characterized by the incomplete development of the germinal epithelium of the seminiferous tubules, Testicular hypoplasia (TH) leads to decreased sperm concentration, increased morphological changes in sperm and azoospermia. Economic losses resulting from the disposal of affected bulls reduce the efficiency of meat production systems. A genome-wide association study and functional analysis were performed to identify genomic windows and the underlying positional candidate genes associated with TH in Nellore cattle. Phenotypic and pedigree data from 207,195 animals and genotypes (461,057 single nucleotide polymorphism, SNP) from 17,326 sires were used in this study. TH was evaluated as a binary trait measured at 18 months of age. A possible correlated response on TH resulting from the selection for scrotal circumference was evaluated by using a two-trait analysis. Thus, estimated breeding values were calculated by fitting a linear-threshold animal model in a Bayesian approach. The SNP effects were estimated using the weighted single-step genomic BLUP method. Twelve non-overlapping windows of 20 adjacent SNP that explained more than 1% of the additive genetic variance were selected for candidate gene annotation. Functional and gene prioritization analysis of the candidate genes identified genes (KHDRBS3, GPX5, STAR, ERLIN2), which might play an important role in the expression of TH due to their known roles in the spermatogenesis process, synthesis of steroids and lipid metabolism.

Genomic structural plasticity of rodent-associated Bartonella in nature.

Rodent-associated Bartonella species have shown a remarkable genetic diversity and pathogenic potential. To further explore the extent of the natural intraspecific genomic variation and its potential role as an evolutionary driver, we focused on a single genetically diverse Bartonella species, Bartonella krasnovii, which circulates among gerbils and their associated fleas. Twenty genomes from 16 different B. krasnovii genotypes were fully characterized through a genome sequencing assay (using short and long read sequencing), pulse field gel electrophoresis (PFGE), and PCR validation. Genomic analyses were performed in comparison to the B. krasnovii strain OE 1-1. While, single nucleotide polymorphism represented only a 0.3% of the genome variation, structural diversity was identified in these genomes, with an average of 51 ± 24 structural variation (SV) events per genome. Interestingly, a large proportion of the SVs (>40%) was associated with prophages. Further analyses revealed that most of the SVs, and prophage insertions were found at the chromosome replication termination site (ter), suggesting this site as a plastic zone of the B. krasnovii chromosome. Accordingly, six genomes were found to be unbalanced, and essential genes near the ter showed a shift between the leading and lagging strands, revealing the SV effect on these genomes. In summary, our findings demonstrate the extensive genomic diversity harbored by wild B. krasnovii strains and suggests that its diversification is initially promoted by structural changes, probably driven by phages. These events may constantly feed the system with novel genotypes that ultimately lead to inter- and intraspecies competition and adaptation.

Genetics and genomics of uniformity and resilience in livestock and aquaculture species: A review.

Genetic control of residual variance offers opportunities to increase uniformity and resilience of livestock and aquaculture species. Improving uniformity and resilience of animals will improve health and welfare of animals and lead to more homogenous products. Our aims in this review were to summarize the current models and methods to study genetic control of residual variance, genetic parameters and genomic results for residual variance and discuss future research directions. Typically, the genetic coefficient of variation is high (median = 0.27; range 0-0.86) and the heritability of residual variance is low (median = 0.01; range 0-0.10). Higher heritabilities can be achieved when increasing the number of records per animal. Divergent selection experiments have supported the feasibility of selecting for high or low residual variance. Genomic studies have revealed associations in regions related to stress, including those from the heat shock protein family. Although the number of studies is growing, genetic control of residual variance is still poorly understood, but big data and genomics offer great opportunities.

Association of Copy Number Variation at Intron 3 of HMGA2 With Navel Length in Bos indicus.

Navel injuries caused by friction against the pasture can promote infection, reproductive problems and costly treatments in beef cattle raised in extensive systems. A haplotype-based genome-wide association study (GWAS) was performed for visual scores of navel length at yearling in Nellore cattle (Bos indicus) using data from 2,016 animals and 503,088 single nucleotide polymorphism (SNP) markers. The strongest signal (p = 1.01 × 10-9) was found on chromosome 5 spanning positions 47.9-48.2 Mbp. This region contains introns 3 and 4 and exons 4 and 5 of the high mobility group AT-hook 2 gene (HMGA2). Further inspection of the region with whole genome sequence data of 21 Nellore bulls revealed correlations between counts of the significant haplotype and copy number gains of a ∼6.2 kbp segment of intron 3 of HMGA2. Analysis of genome sequences from five African B. indicus and four European Bos taurus breeds revealed that the copy number variant (CNV) is indicine-specific. This intronic CNV was then validated through quantitative polymerase chain reaction (qPCR) using Angus animals as copy neutral controls. Importantly, the CNV was not detectable by means of conventional SNP-based GWAS or SNP probe intensity analyses. Given that HMGA2 affects the expression of the insulin-like growth factor 2 gene (IGF2) together with the pleomorphic adenoma gene 1 (PLAG1), and that the latter has been repeatedly shown to be associated with quantitative traits of economic importance in cattle, these findings highlight the emerging role of variants impacting the insulin-like growth factor pathway to cattle breeding.

Genomic regions underlying uniformity of yearling weight in Nellore cattle evaluated under different response variables.

BACKGROUND: In livestock, residual variance has been studied because of the interest to improve uniformity of production. Several studies have provided evidence that residual variance is partially under genetic control; however, few investigations have elucidated genes that control it. The aim of this study was to identify genomic regions associated with within-family residual variance of yearling weight (YW; N = 423) in Nellore bulls with high density SNP data, using different response variables. For this, solutions from double hierarchical generalized linear models (DHGLM) were used to provide the response variables, as follows: a DGHLM assuming non-null genetic correlation between mean and residual variance (rmv ≠ 0) to obtain deregressed EBV for mean (dEBVm) and residual variance (dEBVv); and a DHGLM assuming rmv = 0 to obtain two alternative response variables for residual variance, dEBVv_r0 and log-transformed variance of estimated residuals (ln_[Formula: see text]). RESULTS: The dEBVm and dEBVv were highly correlated, resulting in common regions associated with mean and residual variance of YW. However, higher effects on variance than the mean showed that these regions had effects on the variance beyond scale effects. More independent association results between mean and residual variance were obtained when null rmv was assumed. While 13 and 4 single nucleotide polymorphisms (SNPs) showed a strong association (Bayes Factor > 20) with dEBVv and ln_[Formula: see text], respectively, only suggestive signals were found for dEBVv_r0. All overlapping 1-Mb windows among top 20 between dEBVm and dEBVv were previously associated with growth traits. The potential candidate genes for uniformity are involved in metabolism, stress, inflammatory and immune responses, mineralization, neuronal activity and bone formation. CONCLUSIONS: It is necessary to use a strategy like assuming null rmv to obtain genomic regions associated with uniformity that are not associated with the mean. Genes involved not only in metabolism, but also stress, inflammatory and immune responses, mineralization, neuronal activity and bone formation were the most promising biological candidates for uniformity of YW. Although no clear evidence of using a specific response variable was found, we recommend consider different response variables to study uniformity to increase evidence on candidate regions and biological mechanisms behind it.

Genome-wide association study using haplotype alleles for the evaluation of reproductive traits in Nelore cattle.

Zebu cattle (Bos taurus indicus) are highly adapted to tropical regions. However, females reach puberty after taurine heifers, which affects the economic efficiency of beef cattle breeding in the tropical regions. The aims of this study were to establish associations between the haplotype alleles of the bovine genome and age at first calving (AFC) in the Nelore cattle, and to identify the genes and quantitative trait loci (QTL) related to this phenotype. A total of 2,273 Nelore cattle (995 males and 1,278 females) genotyped using the Illumina BovineHD BeadChip were used in the current study. The association analysis included females with valid first calving records as well as open heifers. Linkage disequilibrium (LD) analysis among the markers was performed using blocks of 5, 10, and 15 markers, which were determined by sliding windows shifting one marker at a time. Then, the haplotype block size to be used in the association study was chosen based on the highest r2 average among the SNPs in the block. The five HapAlleles most strongly associated with the trait (top five) were considered as significant associations. The results of the analysis revealed four genomic regions related to AFC, which overlapped with 20 QTL of the reproductive traits reported previously. Furthermore, there were 19 genes related to reproduction in those regions. In conclusion, the use of haplotypes allowed the detection of chromosomal regions associated with AFC in Nelore cattle, and provided the basis for elucidating the mechanisms underlying this trait.

Trait-specific long-term consequences of genomic selection in beef cattle.

Simulation studies allow addressing consequences of selection schemes, helping to identify effective strategies to enable genetic gain and maintain genetic diversity. The aim of this study was to evaluate the long-term impact of genomic selection (GS) in genetic progress and genetic diversity of beef cattle. Forward-in-time simulation generated a population with pattern of linkage disequilibrium close to that previously reported for real beef cattle populations. Different scenarios of GS and traditional pedigree-based BLUP (PBLUP) selection were simulated for 15 generations, mimicking selection for female reproduction and meat quality. For GS scenarios, an alternative selection criterion was simulated (wGBLUP), intended to enhance long-term gains by attributing more weight to favorable alleles with low frequency. GS allowed genetic progress up to 40% greater than PBLUP, for female reproduction and meat quality. The alternative criterion wGBLUP did not increase long-term response, although allowed reducing inbreeding rates and loss of favorable alleles. The results suggest that GS outperforms PBLUP when the selected trait is under less polygenic background and that attributing more weight to low-frequency favorable alleles can reduce inbreeding rates and loss of favorable alleles in GS.

A PLAG1 mutation contributed to stature recovery in modern cattle.

The recent evolution of cattle is marked by fluctuations in body size. Height in the Bos taurus lineage was reduced by a factor of ~1.5 from the Neolithic to the Middle Ages, and increased again only during the Early Modern Ages. Using haplotype analysis, we found evidence that the bovine PLAG1 mutation (Q) with major effects on body size, weight and reproduction is a >1,000 years old derived allele that increased rapidly in frequency in Northwestern European B. taurus between the 16th and 18th centuries. Towards the 19th and 20th centuries, Q was introgressed into non-European B. taurus and Bos indicus breeds. These data implicate a major role of Q in recent changes in body size in modern cattle, and represent one of the first examples of a genomic sweep in livestock that was driven by selection on a complex trait.

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.

Serological detection of Toxoplasma gondii, Leishmania infantum and Neospora caninum in cats from an area endemic for leishmaniasis in Brazil.

An investigation was made into the occurrence of antibodies to Toxoplasma gondii, Leishmania infantum and Neospora caninum in 151 domestic cats, based on the indirect fluorescent antibody test (IFAT). Serum samples were collected from 151 domestic cats (65 free-roaming and 86 domiciled cats; 55 males and 96 females) in Campo Grande, Mato Grosso do Sul, Brazil between January and April 2013. IgG antibodies to T. gondii, L. infantum and N. caninum were found, respectively, in 49 (32.5%), 34 (22.5%) and 10 (6.6%) sampled cats. A positive correlation was found between T. gondii and N. caninum, T. gondii and L. infantum, and N. caninum and L. infantum (p <0.05) infections. Also, a significant interaction was identified between gender and area of activity on the probability of T. gondii (p = 0.0324) infection. However, no significant interaction was observed between gender and area of activity on infections by either N. caninum or L. infantum. This study showed that cats from an area endemic for visceral leishmaniasis in Brazil are exposed to three different protozoans, two of which are causal agents of important zoonosis.

Serological detection of Toxoplasma gondii, Leishmania infantum and Neospora caninum in cats from an area endemic for leishmaniasis in Brazil / Detecção sorológica de Toxoplasma gondii, Leishmania infantum e Neospora caninum em gatos de uma área endêmica para leishmaniose no Brasil

An investigation was made into the occurrence of antibodies to Toxoplasma gondii, Leishmania infantum and Neospora caninum in 151 domestic cats, based on the indirect fluorescent antibody test (IFAT). Serum samples were collected from 151 domestic cats (65 free-roaming and 86 domiciled cats; 55 males and 96 females) in Campo Grande, Mato Grosso do Sul, Brazil between January and April 2013. IgG antibodies to T. gondii, L. infantum and N. caninum were found, respectively, in 49 (32.5%), 34 (22.5%) and 10 (6.6%) sampled cats. A positive correlation was found between T. gondii and N. caninum, T. gondii and L. infantum, and N. caninum and L. infantum (p <0.05) infections. Also, a significant interaction was identified between gender and area of activity on the probability of T. gondii (p = 0.0324) infection. However, no significant interaction was observed between gender and area of activity on infections by either N. caninum or L. infantum. This study showed that cats from an area endemic for visceral leishmaniasis in Brazil are exposed to three different protozoans, two of which are causal agents of important zoonosis.

O presente estudo teve como objetivo investigar a ocorrência de anticorpos anti-Toxoplasma gondii, Leishmania infantum e Neospora caninum, em 151 gatos, por meio da Reação de Imunofluorescência Indireta (RIFI). Entre os meses de janeiro e abril de 2013, amostras de soro foram coletadas de 151 gatos domésticos (65 gatos errantes e 86 gatos domiciliados; 55 machos e 96 fêmeas), de Campo Grande, Mato Grosso do Sul, Brasil. Anticorpos IgG anti-T. gondii, anti-L. infantum e anti-N. caninum foram encontrados em 49 (32,5%), 34 (22,5%) e 10 (6,6%) gatos amostrados, respectivamente. Verificou-se uma associação estatisticamente significativa entre as infecções por T. gondii e N. caninum, T. gondii e L. infantum e N. caninum e Leishmania infantum (p <0,05). Além disso, foi observada uma interação significativa entre sexo, área de atividade na probabilidade de infecção por T. gondii (p = 0,0324). No entanto, não foi observada interação significativa entre sexo e área de atividade nas infecções por N. caninum e L. infantum. Este estudo mostrou que os gatos de uma área endêmica brasileira para leishmaniose visceral são expostos a três diferentes protozoários, sendo dois deles importantes agentes zoonóticos.

Herd-of-origin effect on the post-weaning performance of centrally tested Nellore beef cattle.

The objective of a performance test station is to evaluate the performance of potential breeding bulls earlier in order to decrease the generation interval and increase genetic gain as well. This study evaluates the herd-of-origin influence on end-of-test weight (ETW), average daily weight gain during testing (ADG), average daily weight gain during the adjustment period (ADGadj), rib eye area (REA), marbling (MARB), subcutaneous fat thickness (SFT), conformation (C), early finishing (EF), muscling (M), navel (N) and temperament (T) scores, and scrotal circumference (SC) of Nellore cattle that underwent a performance test. We evaluated 664 animals that participated in the performance tests conducted at the Center for Performance CRV Lagoa between 2007 and 2012. Components of variance for each trait were estimated by an animal model (model 1), using the restricted maximum likelihood method. An alternative animal model (model 2) included, in addition to the fixed effects present in S1, the non-correlated random effect of herd-year (HY). A significant HY effect was observed on ETW, REA, SFT, ADGadj, C, and Cw (p < 0.05). The estimated heritability of all traits decreased when the HY effect was included in the model; also, the bull rank, in deciles, changed significantly for traits ETW, REA, SFT, and C. The adjustment period did not completely remove the environmental effect of herd of origin on ETW, REA, SFT, and C. It is recommended that the herd-of-origin effect should be included in the statistical models used to predict the breeding values of the participants of these performance tests.