Correction: Tournaments between markers as a strategy to enhance genomic predictions.

[This corrects the article DOI: 10.1371/journal.pone.0217283.].

Tournaments between markers as a strategy to enhance genomic predictions.

Analysis of a large number of markers is crucial in both genome-wide association studies (GWAS) and genome-wide selection (GWS). However there are two methodological issues that restrict statistical analysis: high dimensionality (p≫n) and multicollinearity. Although there are methodologies that can be used to fit models for data with high dimensionality (eg, the Bayesian Lasso), a big problem that can occurs in this cases is that the predictive ability of the model should perform well for the individuals used to fit the model, but should not perform well for other individuals, restricting the applicability of the model. This problem can be circumvent by applying some selection methodology to reduce the number of markers (but keeping the markers associated with the phenotypic trait) before adjusting a model to predict GBVs. We revisit a tournament-based strategy between marker samples, where each sample has good statistical properties for estimation: n>p and low collinearity. Such tournaments are elaborated using multiple linear regression to eliminate markers. This method is adapted from previous works found in the literature. We used simulated data as well as real data derived from a study with SNPs in beef cattle. Tournament strategies not only circumvent the p≫n issue, but also minimize spurious associations. For real data, when we selected a few more than 20 markers, we obtained correlations greater than 0.70 between predicted Genomic Breeding Values (GBVs) and phenotypes in validation groups of a cross-validation scheme; and when we selected a larger number of markers (more than 100), the correlations exceeded 0.90, showing the efficiency in identifying relevant SNPs (or segregations) for both GWAS and GWS. In the simulation study, we obtained similar results.

Candidate genes for male and female reproductive traits in Canchim beef cattle.

BACKGROUND: Beef cattle breeding programs in Brazil have placed greater emphasis on the genomic study of reproductive traits of males and females due to their economic importance. In this study, genome-wide associations were assessed for scrotal circumference at 210 d of age, scrotal circumference at 420 d of age, age at first calving, and age at second calving, in Canchim beef cattle. Data quality control was conducted resulting in 672,778 SNPs and 392 animals. RESULTS: Associated SNPs were observed for scrotal circumference at 420 d of age (435 SNPs), followed by scrotal circumference at 210 d of age (12 SNPs), age at first calving (six SNPs), and age at second calving (four SNPs). We investigated whether significant SNPs were within genic or surrounding regions. Biological processes of genes were associated with immune system, multicellular organismal process, response to stimulus, apoptotic process, cellular component organization or biogenesis, biological adhesion, and reproduction. CONCLUSIONS: Few associations were observed for scrotal circumference at 210 d of age, age at first calving, and age at second calving, reinforcing their polygenic inheritance and the complexity of understanding the genetic architecture of reproductive traits. Finding many associations for scrotal circumference at 420 d of age in various regions of the Canchim genome also reveals the difficulty of targeting specific candidate genes that could act on fertility; nonetheless, the high linkage disequilibrium between loci herein estimated could aid to overcome this issue. Therefore, all relevant information about genomic regions influencing reproductive traits may contribute to target candidate genes for further investigation of causal mutations and aid in future genomic studies in Canchim cattle to improve the breeding program.

Study on the introgression of beef breeds in Canchim cattle using single nucleotide polymorphism markers.

The aim of this study was to evaluate the level of introgression of breeds in the Canchim (CA: 62.5% Charolais-37.5% Zebu) and MA genetic group (MA: 65.6% Charolais-34.4% Zebu) cattle using genomic information on Charolais (CH), Nelore (NE), and Indubrasil (IB) breeds. The number of animals used was 395 (CA and MA), 763 (NE), 338 (CH), and 37 (IB). The Bovine50SNP BeadChip from Illumina panel was used to estimate the levels of introgression of breeds considering the Maximum likelihood, Bayesian, and Single Regression method. After genotype quality control, 32,308 SNPs were considered in the analysis. Furthermore, three thresholds to prune out SNPs in linkage disequilibrium higher than 0.10, 0.05, and 0.01 were considered, resulting in 15,286, 7,652, and 1,582 SNPs, respectively. For k = 2, the proportion of taurine and indicine varied from the expected proportion based on pedigree for all methods studied. For k = 3, the Regression method was able to differentiate the animals in three main clusters assigned to each purebred breed, showing more reasonable according to its biological viewpoint. Analyzing the data considering k = 2 seems to be more appropriate for Canchim-MA animals due to its biological interpretation. The usage of 32,308 SNPs in the analyses resulted in similar findings between the estimated and expected breed proportions. Using the Regression approach, a contribution of Indubrasil was observed in Canchim-MA when k = 3 was considered. Genetic parameter estimation could account for this breed composition information as a source of variation in order to improve the accuracy of genetic models. Our findings may help assemble appropriate reference populations for genomic prediction for Canchim-MA in order to improve prediction accuracy. Using the information on the level of introgression in each individual could also be useful in breeding or crossing design to improve individual heterosis in crossbred cattle.

Selection signatures in Canchim beef cattle.

BACKGROUND: Recent technological advances in genomics have allowed the genotyping of cattle through single nucleotide polymorphism (SNP) panels. High-density SNP panels possess greater genome coverage and are useful for the identification of conserved regions of the genome due to selection, known as selection signatures (SS). The SS are detectable by different methods, such as the extended haplotype homozygosity (EHH); and the integrated haplotype score (iHS), which is derived from the EHH. The aim of this study was to identify SS regions in Canchim cattle (composite breed), genotyped with high-density SNP panel. RESULTS: A total of 687,655 SNP markers and 396 samples remained for SS analysis after the genotype quality control. The iHS statistic for each marker was transformed into piHS for better interpretation of the results. Chromosomes BTA5 and BTA14 showed piHS > 5, with 39 and nine statistically significant SNPs (P < 0.00001), respectively. For the candidate selection regions, iHS values were computed across the genome and averaged within non-overlapping windows of 500 Kb. We have identified genes that play an important role in metabolism, melanin biosynthesis (pigmentation), and embryonic and bone development. CONCLUSIONS: The observation of SS indicates that the selection processes performed in Canchim, as well as in the founder breeds (i.e. Charolais), are maintaining specific genomic regions, particularly on BTA5 and BTA14. These selection signatures regions could be associated with Canchim characterization.

Effect of IGF1, GH, and PIT1 markers on the genetic parameters of growth and reproduction traits in Canchim cattle.

The availability of dense genomic information has increased genome-wide association studies for the bovine species; however research to assess the effect of single genes on production traits is still important to elucidate the genes functions. On this study the association of IGF1, GH, and PIT1 markers with growth and reproductive traits (birth weight, weaning weight, weight at 12 and 18 months of age, preweaning average daily weight gain, age and weight at first calving, and scrotal circumference at 12 and 18 months of age) were assessed by means of the variance component approach. The phenotypes were adjusted and then analyzed under two animal models, one which considered the polygenic and genotype (IGF1, GH or PIT1 markers) effects (Model 1), and the other which considers only the polygenic effect (Model 2). When the likelihood ratio test and the Bonferroni correction was applied at 5 % significance level, the genetic markers for the IGF1, GH, and PIT1 genes did not influence significantly the traits (p > 0.002). However, evidence of association of IGF1 with birth weight (p = 0.06) and GH with weight at first calving (p = 0.03) and with weight at 12 months of age (p = 0.08) was observed. In conclusion we could not confirm the associations between IGF1, GH, and PIT1 and growth traits that were previously reported in Canchim cattle, and no association was observed between these genes and reproductive traits. Future studies involving functional markers of IGF1, GH and PIT1 genes may help to clarify the role of these genes in growth and reproductive processes.

Linkage disequilibrium and haplotype block structure in a composite beef cattle breed.

BACKGROUND: The development of linkage disequilibrium (LD) maps and the characterization of haplotype block structure at the population level are useful parameters for guiding genome wide association (GWA) studies, and for understanding the nature of non-linear association between phenotypes and genes. The elucidation of haplotype block structure can reduce the information of several single nucleotide polymorphisms (SNP) into the information of a haplotype block, reducing the number of SNPs in a coherent way for consideration in GWA and genomic selection studies. RESULTS: The maximum average LD, measured by r2 varied between 0.33 to 0.40 at a distance of < 2.5 kb, and the minimum average values of r2 varied between 0.05 to 0.07 at distances ranging from 400 to 500 kb, clearly showing that the average r2 reduced with the increase in SNP pair distances. The persistence of LD phase showed higher values at shorter genomic distances, decreasing with the increase in physical distance, varying from 0.96 at a distance of < 2.5 kb to 0.66 at a distance from 400 to 500 kb. A total of 78% of all SNPs were clustered into haplotype blocks, covering 1,57 Mb of the total autosomal genome size. CONCLUSIONS: This study presented the first high density linkage disequilibrium map and haplotype block structure for a composite beef cattle population, and indicates that the high density SNP panel over 700 k can be used for genomic selection implementation and GWA studies for Canchim beef cattle.

Genetic analyses of days to calving and their relationships with other traits in a Canchim cattle herd

Heritabilities and genetic correlations in a Canchim beef cattle herd were estimated using data on the following traits: male scrotal circumference at twelve months (SC12); days to first calving (DFC) for heifers; days to calving (DC) for cows; male and female weight (W) at twelve months (W12); heifer weight at the start of the first breeding season (WFBS) and at first calving (WFC); and cow weight at the start of the breeding season (WBS) and at calving (WC). Analyses of the DFC and DC traits were carried out excluding and including penalized (DFC P and DC P) non-calving females. The restricted maximum likelihood method was used, applying one-trait models for the DFC and DC analyses and two-trait models for analyses of DFC and DC combined with the other traits studied. Statistical models included fixed and additive direct random effects for all traits, maternal permanent environmental random effect for SC12 and W12, and the animal permanent environmental random effect for DC P, WBS and WC. We found that DFC and DC values can be improved by selecting for an increase in the SC12. Genetic correlations between DFC and W12 and between DC and W12 indicated that selection for increased W12 may increase DFC but does not produce significantly correlated responses in DC. Associations of the other body weight traits with DC and DFC suggest that heavier females experience lower reproductive performance.

Artificial infestation of Boophilus microplus in beef cattle heifers of four genetic groups

Resistance of beef cattle heifers to the cattle tick Boophilus microplus was evaluated by artificial infestation of 66 beef cattle heifers of the following genetic groups: 16 Nelore (NE), 18 Canchim x Nelore (CN), 16 Angus x Nelore (AN) and 16 Simmental x Nelore (SN). The animals, with a mean age of 16.5 months, were maintained with no chemical tick control in a Brachiaria decumbens pasture. Four artificial infestations with 20,000 B. microplus larvae were carried out 14 days apart and from day 18 to day 22 of each infestation the number of engorged female ticks (> 4.5 mm) was counted on the left side of each heifer. Data were analyzed as the percentage of return (PR = percentage of ticks counted relative to the number infested), transformed to (PR)», and as log10 (Cij + 1), in which Cij is the number of ticks in each infestation, using the least squares method with a model that included the effects of genetic group (GG), animal within GG (error a), infestation number (I), GG x I and the residual (error b). Results indicated a significant GG x I interaction, because AN and SN heifers had a higher percentage of return than CN and NE heifers, while CN heifers showed a higher percentage of return than the NE heifers only in infestations 3 and 4. Transformed percentages of return were NE = 0.35 ± 0.06, AN = 0.89 ± 0.06, CN = 0.54 ± 0.05 and SN = 0.85 ± 0.06.

Molecular marker heterozygosities and genetic distances as correlates of production traits in F1 bovine crosses

Several studies have investigated the relationship between heterozygosity, genetic distance and production traits. The objective of the present study was to evaluate the influence of the degree of heterozygosity and genetic distance on growth, carcass and reproductive related features in F1 bovine crosses. We tested 10 polymorphic markers in 330 purebred cattle (Nelore, Canchim, Aberdeen Angus and Simental) and 256 crossbred cattle belonging to four crossbred groups. Individual heterozygosities (Hi) and multilocus genetic similarity (Dm) were estimated and used in correlation analysis against individual phenotypic measurements. Significant (p < 0.05) Hi effects occurred for birth weight, 15 to 18 month weight, hot carcass weight and longissimus rib eye area. The extent to which increased heterozygosity (deltaH) in F1 crosses can be predicted from the genetic distance of parental breeds was also investigated using Nei's standard genetic distance (Ds) and standard heterozygosity (Hs). High correlations were found between deltaHi, deltaHs and the Ds of the parental breeds. Our results suggest that heterozygosity of the ten molecular markers used in this study may affect live weight during at least one growth phase. Parental genetic distance was a suitable predictor of the degree of progeny heterozygosity.

Association of GH and IGF-1 polymorphisms with growth traits in a synthetic beef cattle breed

The Canchim beef cattle (5/8 Charolais + 3/8 Zebu) has been selected for meat production in Brazil since late 1950. In the present work the effects of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) polymorphisms were investigated in 688 animals born between 1998 and 2000. These animals belonged to two genetic groups, i.e., traditional and new lineages. Genotype effects on expected breeding values for birth weight (BW), weaning weight (WW) and yearling weight (YW) were investigated by the least square method. Significant effects were found for GH genotype on YW (p < 0.05), with positive effects associated with the LV (leucine/valine) genotype. For IGF-1 genotypes, significant effects were found on BW (p < 0.01) and YW (p < 0.01). Average substitution effects for IGF-1 alleles estimated by regression analysis suggested a positive effect of the IGF-1 225 bp allele on BW and of the 229 bp allele on YW.

Genetic analysis of the infestation of females of the Caracu cattle breed by Horn Fly (Haematobia irritans irritans) L. (Diptera, Muscidae)

The objective of this study was to evaluate environmental factors that affect infestation of Caracu cattle breed by horn fly (Haematobia irritans) and to estimate genetic parameters for level of infestation. Infestation was evaluated on females from two herds in two consecutive years. Total number of flies on animals (FC) was counted, an infestation score (FS: 1 to 5) was recorded according to the estimated number of flies on animals, and number of parasites in photographs (FF) taken when the animals were evaluated was also counted. On each animal from one to eight observations were taken. A total of 3,836, 2,751 and 3,754 records from 718 animals were obtained for FC, FF and FS, respectively. The incidence of flies was lower during winter and higher during summer, and the thicker the hair coat of the animal the greater the infestation. Heritabilities and repeatabilities were equal to 0.10 and 0.10, 0.08 and 0.12, and 0.06 and 0.08, for FC, FF and FS, respectively. Findings indicate that selection for FC will result in low genetic progress and that animals should be evaluated more than once for selection purposes.

Tendência genética em pesos de bovinos da raça Nelore Mocha no Brasil / Genetic trends for body weight of polled Nellore cattle in Brazil

Uma amostra de 5924 animais, progênies de 28 touros, da raça Nelore Mocha, distribuídos em 3 regiões geográficas do Brasil (Sudeste, Nordeste e Centro-oeste), nascidos no período de 1981 a 1992, foi objeto deste estudo, no qual foram avaliadas as mudanças fenotípicas, genéticas e de meio sobre o peso aos 205 (P205), 365 (P365) e 550 (P550) dias de idade, para os conjuntos das regiões. A mudança fenotípica anual foi de 0,475 kg, 0,258 kg e 0,188 kg, respectivamente, para P205, P365 e P550. As mudanças genéticas estimadas foram de 1,518 kg/ano (P205), 2,206 kg/ano (P365) e 3,142 kg/ano (P550). As estimativas de mudanças de ambiente foram de -1,043 kg/ano (P205), -1,948 kg/ano (P365), e -2,254 kg/ano (P550).

Biometria testicular de touros Nelore (Bos taurus indicus) e touros cruzados Nelore-europeu (Bos taurus indicus x Bos taurus taurus) aos 20 e 24 meses de idade / Testicular biometry of Nellore (Bos taurus indicus) and crossbred bulls (Bos taurus indicus x Bos taurus taurus) at 20 and 24 months of age

O objetivo deste trabalho foi estudar os efeitos da idade, do grupo genético e da interaçäo entre idade e grupo genético, sobre as biometrias testiculares (circunferência escrotal e consistência testicular) Foram avaliados, aos 20 e 24 meses de idade, 190 touros Nelore e 447 touros cruzados Nelore-europeu. Aos 24 meses os exames foram repetidos. A circunferência escrotal e a consistência testicular foram influenciadas pelo grupo genético, idade e interaçäo grupo genético x idade. Foram encontradas maiores médias de circunferência escrotal e menores de consistência testicular em cruzados que em Nelore, tanto aos 20 quanto aos 24 meses. Correlaçöes entre circunferência escrotal As correlaçöes entre circunferência escrotal e idade, observadas no presente experimento, foram baixas para os touros Nelore aos 20 meses e aos 24 meses assim como para os cruzados aos 20 meses e aos 24 meses, entretanto, as correlaçöes entre circunferência escrotal e peso corporal foram maiores. As correlaçöes entre consistência testicular e idade e entre consistência testicular e peso corporal foram baixas para a maioria dos cruzados, para os cruzados em conjunto e para os Nelores

Avaliaçäo de sêmen congelado de bovinos. Provas lenta e rápida de termo-resistência: efeitos sobre a fertilidade / Evaluation of frozen bull semen. Quick and slow thermoresistance tests: effects on fertility

O objetivo do presente trabalho foi avaliar a eficiência de sêmen congelado, submetido às provas rápida (45 §C/1 hora) e lenta (38 §C/5 horas) de termo-resistência, sobre a fertilidade de fêmeas da espécie bovina. Cento e dezenove vacas foram selecionadas e divididas em 2 tratamentos. No tratamento 1 foram incluídos 6 grupos de 10 fêmeas, inseminadas com material cuja análise laboratorial revelou motilidade espermática progressiva superior ou igual a 20//, na prova rápida e valor menor a 20//na prova lenta. O tratamento 2 (controle) utilizou 59 vacas distribuídas em 5 grupos de 10 e um grupo de 9, inseminadas com material que, na prova lenta, apresentou 20//de motilidade espermática progressiva e qualquer valor na prova rápida. Apenas uma palheta foi utilizada por estro, tolerando-se até 3 repetiçöes de cio. O diagnóstico de gestaçäo foi realizado por palpaçäo retal, cerca de 60 dias após a última inseminaçäo artificial. Resultados satisfatórios foram alcançados nas taxas de prenhez (TTR/R = 0,793 ñ 0,05 e TTR/L = 0,875 ñ 0,05), näo havendo diferença estatística (P>0,05) quanto ao tipo de provas do termo-resistência. Näo houve diferença significativa (P>0,05) de prenhez de fêmeas inseminadas com material submetido ao teste de termo-resistência rápido, quando a motilidade espermática variou de 20 a 50//