RESUMO
Most deleterious variants are recessive and segregate at relatively low frequency. Therefore, high sample sizes are required to identify these variants. In this study we report a large-scale sequence based genome-wide association study (GWAS) in pigs, with a total of 120,000 Large White and 80,000 Synthetic breed animals imputed to sequence using a reference population of approximately 1,100 whole genome sequenced pigs. We imputed over 20 million variants with high accuracies (R2>0.9) even for low frequency variants (1-5% minor allele frequency). This sequence-based analysis revealed a total of 14 additive and 9 non-additive significant quantitative trait loci (QTLs) for growth rate and backfat thickness. With the non-additive (recessive) model, we identified a deleterious missense SNP in the CDHR2 gene reducing growth rate and backfat in homozygous Large White animals. For the Synthetic breed, we revealed a QTL on chromosome 15 with a frameshift variant in the OBSL1 gene. This QTL has a major impact on both growth rate and backfat, resembling human 3M-syndrome 2 which is related to the same gene. With the additive model, we confirmed known QTLs on chromosomes 1 and 5 for both breeds, including variants in the MC4R and CCND2 genes. On chromosome 1, we disentangled a complex QTL region with multiple variants affecting both traits, harboring 4 independent QTLs in the span of 5 Mb. Together we present a large scale sequence-based association study that provides a key resource to scan for novel variants at high resolution for breeding and to further reduce the frequency of deleterious alleles at an early stage in the breeding program.
Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Humanos , Animais , Suínos/genética , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Fenótipo , Frequência do Gene , Genótipo , Proteínas do Citoesqueleto/genéticaRESUMO
Heat stress is an important issue in the global dairy industry. In tropical areas, an alternative to overcome heat stress is the use of crossbred animals or synthetic breeds, such as the Girolando. In this study, we performed a genome-wide association study (GWAS) and post-GWAS analyses for heat stress in an experimental Gir × Holstein F2 population. Rectal temperature (RT) was measured in heat-stressed F2 animals, and the variation between 2 consecutive RT measurements (ΔRT) was used as the dependent variable. Illumina BovineSNP50v1 BeadChip (Illumina Inc., San Diego, CA) and single-SNP approach were used for GWAS. Post-GWAS analyses were performed by gene ontology terms enrichment and gene-transcription factor (TF) networks, generated from enriched TF. The breed origin of marker alleles in the F2 population was assigned using the breed of origin of alleles (BOA) approach. Heritability and repeatability estimates (± standard error) for ΔRT were 0.13 ± 0.08 and 0.29 ± 0.06, respectively. Association analysis revealed 6 SNP significantly associated with ΔRT. Genes involved with biological processes in response to heat stress effects (LIF, OSM, TXNRD2, and DGCR8) were identified as putative candidate genes. After performing the BOA approach, the 10% of F2 animals with the lowest breeding values for ΔRT were classified as low-ΔRT, and the 10% with the highest breeding values for ΔRT were classified as high-ΔRT. On average, 49.4% of low-ΔRT animals had 2 alleles from the Holstein breed (HH), and 39% had both alleles from the Gir breed (GG). In high-ΔRT animals, the average proportion of animals for HH and GG were 1.4 and 50.2%, respectively. This study allowed the identification of candidate genes for ΔRT in Gir × Holstein crossbred animals. According to the BOA approach, Holstein breed alleles could be associated with better response to heat stress effects, which could be explained by the fact that Holstein animals are more affected by heat stress than Gir animals and thus require a genetic architecture to defend the body from the deleterious effects of heat stress. Future studies can provide further knowledge to uncover the genetic architecture underlying heat stress in crossbred cattle.
Assuntos
Bovinos/genética , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla/veterinária , Resposta ao Choque Térmico/genética , Locos de Características Quantitativas/genética , Alelos , Animais , Cruzamento , Bovinos/fisiologia , Indústria de Laticínios , Feminino , MasculinoRESUMO
BACKGROUND: This study investigated if the allele effect of a given single nucleotide polymorphism (SNP) for crossbred performance in pigs estimated in a genomic prediction model differs depending on its breed-of-origin, and how these are related to estimated effects for purebred performance. RESULTS: SNP-allele substitution effects were estimated for a commonly used SNP panel using a genomic best linear unbiased prediction model with breed-specific partial relationship matrices. Estimated breeding values for purebred and crossbred performance were converted to SNP-allele effects by breed-of-origin. Differences between purebred and crossbred, and between breeds-of-origin were evaluated by comparing percentage of variance explained by genomic regions for back fat thickness (BF), average daily gain (ADG), and residual feed intake (RFI). From ten regions explaining most additive genetic variance for crossbred performance, 1 to 5 regions also appeared in the top ten for purebred performance. The proportion of genetic variance explained by a genomic region and the estimated effect of a haplotype in such a region were different depending upon the breed-of-origin. To illustrate underlying mechanisms, we evaluated the estimated effects across breeds-of-origin for haplotypes associated to the melanocortin 4 receptor (MC4R) gene, and for the MC4Rsnp itself which is a missense mutation with a known effect on BF and ADG. Although estimated allele substitution effects of the MC4Rsnp mutation were very similar across breeds, explained genetic variance of haplotypes associated to the MC4R gene using a SNP panel that does not include the mutation, was considerably lower in one of the breeds where the allele frequency of the mutation was the lowest. CONCLUSIONS: Similar regions explaining similar additive genetic variance were observed across purebred and crossbred performance. Moreover, there was some overlap across breeds-of-origin between regions that explained relatively large proportions of genetic variance for crossbred performance; albeit that the actual proportion of variance deviated across breeds-of-origin. Results based on a missense mutation in MC4R confirmed that even if a causal locus has similar effects across breeds-of-origin, estimated effects and explained variance in its region using a commonly used SNP panel can strongly depend on the allele frequency of the underlying causal mutation.
Assuntos
Alelos , Genômica , Hibridização Genética/genética , Suínos/genética , Animais , Masculino , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , Receptor Tipo 4 de Melanocortina/genéticaRESUMO
Rhipicephalus (Boophilus) microplus is the main cattle ectoparasite in tropical areas. Gir × Holstein crossbred cows are well adapted to different production systems in Brazil. In this context, we performed genome-wide association study (GWAS) and post-GWAS analyses for R. microplus resistance in an experimental Gir × Holstein F2 population. Single nucleotide polymorphisms (SNP) identified in GWAS were used to build gene networks and to investigate the breed of origin for its alleles. Tick artificial infestations were performed during the dry and rainy seasons. Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA) and single-step BLUP procedure was used for GWAS. Post-GWAS analyses were performed by gene ontology terms enrichment and gene transcription factors networks, generated from enriched transcription factors, identified from the promoter sequences of selected gene sets. The genetic origin of marker alleles in the F2 population was assigned using the breed of origin of alleles approach. Heritability estimates for tick counts were 0.40 ± 0.11 in the rainy season and 0.54 ± 0.11 in the dry season. The top ten 0.5-Mbp windows with the highest percentage of genetic variance explained by SNP markers were found in chromosomes 10 and 23 for both the dry and rainy seasons. Gene network analyses allowed the identification of genes involved with biological processes relevant to immune system functions (TREM1, TREM2, and CD83). Gene-transcription factors network allowed the identification of genes involved with immune functions (MYO5A, TREML1, and PRSS16). In resistant animals, the average proportion of animals showing significant SNPs with paternal and maternal alleles originated from Gir breed was 44.8% whereas the proportion of animals with both paternal and maternal alleles originated from Holstein breed was 11.3%. Susceptible animals showing both paternal and maternal alleles originated from Holstein breed represented 44.6% on average, whereas both paternal and maternal alleles originated from Gir breed animals represented 9.3%. This study allowed us to identify candidate genes for tick resistance in Gir × Holstein crossbreds in both rainy and dry seasons. According to the origin of alleles analysis, we found that most animals classified as resistant showed 2 alleles from Gir breed, while the susceptible ones showed alleles from Holstein. Based on these results, the identified genes may be thoroughly investigated in additional experiments aiming to validate their effects on tick resistance phenotype in cattle.
Assuntos
Doenças dos Bovinos/parasitologia , Resistência à Doença/genética , Estudo de Associação Genômica Ampla/veterinária , Rhipicephalus/fisiologia , Infestações por Carrapato/veterinária , Alelos , Animais , Brasil , Cruzamento , Bovinos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/genética , Feminino , Variação Genética , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Estações do Ano , Especificidade da Espécie , Infestações por Carrapato/epidemiologia , Infestações por Carrapato/genéticaRESUMO
BACKGROUND: Genomic prediction of purebred animals for crossbred performance can be based on a model that estimates effects of single nucleotide polymorphisms (SNPs) in purebreds on crossbred performance. For crossbred performance, SNP effects might be breed-specific due to differences between breeds in allele frequencies and linkage disequilibrium patterns between SNPs and quantitative trait loci. Accurately tracing the breed-of-origin of alleles (BOA) in three-way crosses is possible with a recently developed procedure called BOA. A model that accounts for breed-specific SNP effects (BOA model), has never been tested empirically on a three-way crossbreeding scheme. Therefore, the objectives of this study were to evaluate the estimates of variance components and the predictive accuracy of the BOA model compared to models in which SNP effects for crossbred performance were assumed to be the same across breeds, using either breed-specific allele frequencies ([Formula: see text] model) or allele frequencies averaged across breeds ([Formula: see text] model). In this study, we used data from purebred and three-way crossbred pigs on average daily gain (ADG), back fat thickness (BF), and loin depth (LD). RESULTS: Estimates of variance components for crossbred performance from the BOA model were mostly similar to estimates from models [Formula: see text] and [Formula: see text]. Heritabilities for crossbred performance ranged from 0.24 to 0.46 between traits. Genetic correlations between purebred and crossbred performance ([Formula: see text]) across breeds ranged from 0.30 to 0.62 for ADG and from 0.53 to 0.74 for BF and LD. For ADG, prediction accuracies of the BOA model were higher than those of the [Formula: see text] and [Formula: see text] models, with significantly higher accuracies only for one maternal breed. For BF and LD, prediction accuracies of models [Formula: see text] and [Formula: see text] were higher than those of the BOA model, with no significant differences. Across all traits, models [Formula: see text] and [Formula: see text] yielded similar predictions. CONCLUSIONS: The BOA model yielded a higher prediction accuracy for ADG in one maternal breed, which had the lowest [Formula: see text] (0.30). Using the BOA model was especially relevant for traits with a low [Formula: see text]. In all other cases, the use of crossbred information in models [Formula: see text] and [Formula: see text], does not jeopardize predictions and these models are more easily implemented than the BOA model.
Assuntos
Alelos , Hibridização Genética , Modelos Genéticos , Linhagem , Seleção Artificial , Animais , Polimorfismo de Nucleotídeo Único , Suínos/genéticaRESUMO
After publication of our article [1], we found a typo in the formula to build the genomic relationship matrix using allele frequencies across all genotyped pigs (matrix) and the genomic relationship matrix using breed-specific allele frequencies (matrix), and we noted that the description to this formula is not very clear.
RESUMO
BACKGROUND: Although breeding programs for pigs and poultry aim at improving crossbred performance, they mainly use training populations that consist of purebred animals. For some traits, e.g. residual feed intake, the genetic correlation between purebred and crossbred performance is low and thus including crossbred animals in the training population is required. With crossbred animals, the effects of single nucleotide polymorphisms (SNPs) may be breed-specific because linkage disequilibrium patterns between a SNP and a quantitative trait locus (QTL), and allele frequencies and allele substitution effects of a QTL may differ between breeds. To estimate the breed-specific effects of alleles in a crossbred population, the breed-of-origin of alleles in crossbred animals must be known. This study was aimed at investigating the performance of an approach that assigns breed-of-origin of alleles in real data of three-breed cross pigs. Genotypic data were available for 14,187 purebred, 1354 F1, and 1723 three-breed cross pigs. RESULTS: On average, 93.0 % of the alleles of three-breed cross pigs were assigned a breed-of-origin without using pedigree information and 94.6 % with using pedigree information. The assignment percentage could be improved by allowing a percentage (fr) of the copies of a haplotype to be observed in a purebred population different from the assigned breed-of-origin. Changing fr from 0 to 20 %, increased assignment of breed-of-origin by 0.6 and 0.7 % when pedigree information was and was not used, respectively, which indicates the benefit of setting fr to 20 %. CONCLUSIONS: Breed-of-origin of alleles of three-breed cross pigs can be derived empirically without the need for pedigree information, with 93.7 % of the alleles assigned a breed-of-origin. Pedigree information is useful to reduce computation time and can slightly increase the percentage of assignments. Knowledge on the breed-of-origin of alleles allows the use of models that implement breed-specific effects of SNP alleles in genomic prediction, with the aim of improving selection of purebred animals for crossbred offspring performance.
Assuntos
Alelos , Cruzamento , Sus scrofa/genética , Animais , Cruzamentos Genéticos , Frequência do Gene , Genótipo , Haplótipos , Desequilíbrio de Ligação , Modelos Genéticos , Linhagem , Polimorfismo de Nucleotídeo Único , Análise de Componente Principal , Locos de Características QuantitativasRESUMO
BACKGROUND: For some species, animal production systems are based on the use of crossbreeding to take advantage of the increased performance of crossbred compared to purebred animals. Effects of single nucleotide polymorphisms (SNPs) may differ between purebred and crossbred animals for several reasons: (1) differences in linkage disequilibrium between SNP alleles and a quantitative trait locus; (2) differences in genetic backgrounds (e.g., dominance and epistatic interactions); and (3) differences in environmental conditions, which result in genotype-by-environment interactions. Thus, SNP effects may be breed-specific, which has led to the development of genomic evaluations for crossbred performance that take such effects into account. However, to estimate breed-specific effects, it is necessary to know breed origin of alleles in crossbred animals. Therefore, our aim was to develop an approach for assigning breed origin to alleles of crossbred animals (termed BOA) without information on pedigree and to study its accuracy by considering various factors, including distance between breeds. RESULTS: The BOA approach consists of: (1) phasing genotypes of purebred and crossbred animals; (2) assigning breed origin to phased haplotypes; and (3) assigning breed origin to alleles of crossbred animals based on a library of assigned haplotypes, the breed composition of crossbred animals, and their SNP genotypes. The accuracy of allele assignments was determined for simulated datasets that include crosses between closely-related, distantly-related and unrelated breeds. Across these scenarios, the percentage of alleles of a crossbred animal that were correctly assigned to their breed origin was greater than 90 %, and increased with increasing distance between breeds, while the percentage of incorrectly assigned alleles was always less than 2 %. For the remaining alleles, i.e. 0 to 10 % of all alleles of a crossbred animal, breed origin could not be assigned. CONCLUSIONS: The BOA approach accurately assigns breed origin to alleles of crossbred animals, even if their pedigree is not recorded.
Assuntos
Cruzamento , Genômica/métodos , Hibridização Genética , Gado/genética , Modelos Genéticos , Alelos , Animais , Simulação por Computador , Feminino , Genótipo , Haplótipos , Desequilíbrio de Ligação , Masculino , Linhagem , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Sus scrofa/genéticaRESUMO
BACKGROUND: Cryptorchidism and scrotal/inguinal hernia are the most frequent congenital defects in pigs. Identification of genomic regions that control these congenital defects is of great interest to breeding programs, both from an animal welfare point of view as well as for economic reasons. The aim of this genome-wide association study (GWAS) was to identify single nucleotide polymorphisms (SNPs) that are strongly associated with these congenital defects. Genotypes were available for 2570 Large White (LW) and 2272 Landrace (LR) pigs. Breeding values were estimated based on 1 359 765 purebred and crossbred male offspring, using a binary trait animal model. Estimated breeding values were deregressed (DEBV) and taken as the response variable in the GWAS. RESULTS: Heritability estimates were equal to 0.26 ± 0.02 for cryptorchidism and to 0.31 ± 0.01 for scrotal/inguinal hernia. Seven and 31 distinct QTL regions were associated with cryptorchidism in the LW and LR datasets, respectively. The top SNP per region explained between 0.96% and 1.10% and between 0.48% and 2.77% of the total variance of cryptorchidism incidence in the LW and LR populations, respectively. Five distinct QTL regions associated with scrotal/inguinal hernia were detected in both LW and LR datasets. The top SNP per region explained between 1.22% and 1.60% and between 1.15% and 1.46% of the total variance of scrotal/inguinal hernia incidence in the LW and LR populations, respectively. For each trait, we identified one overlapping region between the LW and LR datasets, i.e. a region on SSC8 (Sus scrofa chromosome) between 65 and 73 Mb for cryptorchidism and a region on SSC13 between 34 and 37 Mb for scrotal/inguinal hernia. CONCLUSIONS: The use of DEBV in combination with a binary trait model was a powerful approach to detect regions associated with difficult traits such as cryptorchidism and scrotal/inguinal hernia that have a low incidence and for which affected animals are generally not available for genotyping. Several novel QTL regions were detected for cryptorchidism and scrotal/inguinal hernia, and for several previously known QTL regions, the confidence interval was narrowed down.
Assuntos
Criptorquidismo/veterinária , Estudo de Associação Genômica Ampla/métodos , Hérnia Inguinal/veterinária , Polimorfismo de Nucleotídeo Único , Sus scrofa/genética , Animais , Cruzamento , Criptorquidismo/genética , Feminino , Genótipo , Haplótipos/genética , Hérnia Inguinal/genética , Masculino , Locos de Características Quantitativas , SuínosRESUMO
The genome in crossbred animals is a mosaic of genomic regions inherited from the different parental breeds. We previously showed that effects of haplotypes strongly associated with crossbred performance are different depending upon from which parental breed they are inherited, however, the majority of the genomic regions are not or only weakly associated with crossbred performance. Therefore, our objective was to develop a model that distinguishes between selected single nucleotide polymorphisms (SNP) strongly associated with crossbred performance and all remaining SNP. For the selected SNP, breed-specific allele effects were fitted whereas for the remaining SNP it was assumed that effects are the same across breeds (SEL-BOA model). We used data from three purebred populations; S, LR, and LW, and the corresponding crossbred population. We selected SNP that explained together either 5 or 10% of the total crossbred genetic variance for average daily gain in each breed of origin. The model was compared to a model where all SNP-alleles were allowed to have different effects for crossbred performance depending upon the breed of origin (BOA model) and to a model where all SNP-alleles had the same effect for crossbred performance across breeds (G model). Across the models, the heritability for crossbred performance was very similar with values of 0.29-0.30. With the SEL-BOA models, in general, the purebred-crossbred genetic correlation (rpc) for the selected SNP was larger than for the non-selected SNP. For breed LR, the rpc for selected SNP and non-selected SNP estimated with the SEL-BOA 5% and SEL-BOA 10% were very different compared to the rpc estimated with the G or BOA model. For breeds S and LW, there was not a big discrepancy for the rpc estimated with the SEL-BOA models and with the G or BOA model. The BOA model calculates more accurate breeding values of purebred animals for crossbred performance than the G model when rpc differs (≈10%) between the G and the BOA model. Superiority of the SEL-BOA model compared to the BOA model was only observed for SEL-BOA 10% and when rpc for the selected and non-selected SNP differed both (≈20%) from the rpc estimated by the G or BOA model.
RESUMO
In pig breeding, selection commonly takes place in purebred (PB) pigs raised mainly in temperate climates (TEMP) under optimal environmental conditions in nucleus farms. However, pork production typically makes use of crossbred (CB) animals raised in nonstandardized commercial farms, which are located not only in TEMP regions but also in tropical and subtropical regions (TROP). Besides the differences in the genetic background of PB and CB, differences in climate conditions, and differences between nucleus and commercial farms can lower the genetic correlation between the performance of PB in the TEMP (PBTEMP) and CB in the TROP (CBTROP). Genetic correlations (rg) between the performance of PB and CB growing-finishing pigs in TROP and TEMP environments have not been reported yet, due to the scarcity of data in both CB and TROP. Therefore, the present study aimed 1) to verify the presence of genotype × environment interaction (G × E) and 2) to estimate the rg for carcass and growth performance traits when PB and 3-way CB pigs are raised in 2 different climatic environments (TROP and TEMP). Phenotypic records of 217,332 PB and 195,978 CB, representing 2 climatic environments: TROP (Brazil) and TEMP (Canada, France, and the Netherlands) were available for this study. The PB population consisted of 2 sire lines, and the CB population consisted of terminal 3-way cross progeny generated by crossing sires from one of the PB sire lines with commercially available 2-way maternal sow crosses. G × E appears to be present for average daily gain, protein deposition, and muscle depth given the rg estimates between PB in both environments (0.64 to 0.79). With the presence of G × E, phenotypes should be collected in TROP when the objective is to improve the performance of CB in the TROP. Also, based on the rg estimates between PBTEMP and CBTROP (0.22 to 0.25), and on the expected responses to selection, selecting based only on the performance of PBTEMP would give limited genetic progress in the CBTROP. The rg estimates between PBTROP and CBTROP are high (0.80 to 0.99), suggesting that combined crossbred-purebred selection schemes would probably not be necessary to increase genetic progress in CBTROP. However, the calculated responses to selection show that when the objective is the improvement of CBTROP, direct selection based on the performance of CBTROP has the potential to lead to the higher genetic progress compared with indirect selection on the performance of PBTROP.
Assuntos
Interação Gene-Ambiente , Suínos/genética , Animais , Brasil , Cruzamento , Canadá , Cruzamentos Genéticos , Feminino , França , Genótipo , Masculino , Países Baixos , Fenótipo , Suínos/crescimento & desenvolvimento , Suínos/fisiologiaRESUMO
Pig-breeding businesses have resulted in global breeding programs that select pigs to perform well on high-energy high-protein diets, which are traditionally based on corn and soybean meal. Nowadays, there is a shift toward diets based on cereals and co-products, therefore, high dietary inclusion of co-products can modify the expected performance of these pigs. The objective of this study was to evaluate the effect of feeding a cereals-alternative ingredients diet (CA-diet) compared to a corn-soybean meal diet (CS-diet) on the growth performance, feed efficiency, and carcass characteristics of genetically similar growing-finishing gilts and boars. In total, 160 pigs, 80 gilts and 80 boars, coming from 18 litters were used. The pigs were blocked based on litter, to ensure no genetic differences between the 2 treatments. For the starter phase, pigs fed the CA-diet performed in terms of growth, and feed efficiency, as good as the pigs fed CS-diet (P > 0.05). For the grower phase, pigs fed the CA-diet had the same ADFI (P > 0.05), but a lower daily energy intake (ADEI) (P < 0.001), and same growth performance (P > 0.05) than pig fed the CS-diet, therefore pigs fed the CA-diet were more efficient in terms of residual energy intake (REI) (P < 0.001). For the finisher phase, interaction between diet and sex had an effect on ADFI (P < 0.001), ADEI (P < 0.001), ADG (P = 0.010), and lipid deposition (Ld) (P = 0.016). Pigs fed the CA-diet were less efficient than pigs fed the CS-diet, i.e., G:F (P < 0.001), RFI (P < 0.001), and REI (P = 0.007). In general, feeding a CA-diet to pigs showed to improve the ratio between Pd and Ld, especially for boars. Also, pigs fed the CA-diet showed thinner back fat thickness (P < 0.001), same loin depth thickness (P > 0.05), but lower dressing percentage (P < 0.001), than pigs fed the CS-diet.