Bayesian threshold analysis of litter size in sheep

Background: Litter size at birth (LSB) is one of the most important economic traits in sheep and could be used in genetic improvement schemes for meat production. LSB is inherently a categorical trait and should be analysed with threshold models. Objective: Bayesian threshold models were used to analyze sheep LSB to estimate genetic parameters. Methods: Data was based on 7,901 LSB records from 14,968 dams and 682 sires collected from 1986 to 2012 at Makouie Sheep Breeding Station in Iran. Means of posterior distributions (MPDs) of LSB's genetic parameters were estimated, and the best-fitted models were selected using the deviance information criterion. Results: In the repeated measurement analysis, the estimated direct and maternal heritabilities, and permanent environmental effect (±SE), according to the best-fitted model (model 5), were 0.01 (0.010), 0.02 (0.014), and 0.01 (0.011), respectively. In the univariate analysis, the best estimates of direct and maternal heritabilities were 0.12 (0.064) and 0.08 (0.045), respectively. An increasing trend for direct and maternal heritabilities was observed in parity 2 (0.15 (0.082) and 0.25 (0.083), respectively). In the bivariate analysis, the best estimates of direct and maternal heritabilities for LSB were 0.03 (0.027) and 0.22 (0.041), respectively. The direct and maternal genetic correlations among parities were 0.25 (0.054) and 0.12 (0.021), respectively. Conclusions: The results showed a considerable influence of environmental factors on LSB in each parity of sheep; also, statistically different genetic parameters (p<0.05) were obtained from one parity to another, indicating the different and large influences of genetic and environmental factors for each parity.

Antecedentes: El tamaño de la camada al nacer (LSB) es inherentemente un rasgo categórico y debe analizarse con modelos de umbral. El LSB es uno de los rasgos de producción de carne más importantes en las ovejas y podría usarse en esquemas de mejora genética para la producción de carne. Objetivo: Se utilizaron modelos de umbral bayesiano para analizar el tamaño de la camada de ovejas al nacer (LSB) y estimar parámetros genéticos. Métodos: Los datos se basaron en 7.901 registros de LSB de 14.968 ovejas y 682 carneros recolectados de 1986 a 2012 en la estación de cría de ovejas Makouie en Irán. Se estimaron las medias de distribuciones posteriores (MPD) de los parámetros genéticos de LSB y se seleccionaron los modelos mejor ajustados utilizando el criterio de información de desviación. Resultados: En los análisis de medición repetida, la heredabilidad materna y directa estimada y el efecto ambiental permanente (±SE), según el modelo mejor ajustado (modelo 5), fueron 0,01 (0,010), 0,02 (0,014) y 0,01 (0,011), respectivamente. En el análisis univariado, las mejores estimaciones de heredabilidad directa y materna fueron 0,12 (0,064) y 0,08 (0,045), respectivamente. Se observó una tendencia creciente de heredabilidades directas y maternas en la paridad 2 (0,15 (0,082) y 0,25 (0,083), respectivamente). En el análisis bivariado, las mejores estimaciones de heredabilidad directa y materna para LSB fueron 0,03 (0,027) y 0,22 (0,041), respectivamente. Las correlaciones genéticas directas y maternas entre partos fueron 0,25 (0,054) y 0,12 (0,021), respectivamente. Conclusiones: Los resultados mostraron una influencia considerable de los factores ambientales sobre el LSB en cada parto de las ovejas; además, se obtuvieron parámetros genéticos estadísticamente diferentes (p<0.05) de un parto a otro, indicando las diferentes y grandes influencias de factores genéticos y ambientales para cada parto en ovejas. Los resultados de este estudio se pueden precisar aún más utilizando datos de SNP de todo el genoma sobre diferentes partes para manejar una amplia gama de problemas relacionados con la interacción del entorno genético del rasgo LSB.

Antecedentes: O tamanho da ninhada ao nascer (LSB) é inerentemente uma característica categórica e deve ser analisada com modelos de limiar. LSB é uma das características mais importantes de produção de carne em ovinos e pode ser usado em esquemas de melhoramento genético para a produção de carne. Objetivo: Modelos de limiar bayesiano foram usados para analisar o tamanho da ninhada de ovelhas ao nascer (LSB) para estimar parâmetros genéticos. Métodos: Os dados foram baseados em 7.901 registros LSB de 14.968 ovelhas e 682 carneiros coletados de 1986 a 2012 na Estação de Criação de Ovinos Makouie no Irã. Médias de distribuições posteriores (MPDs) dos parâmetros genéticos de LSB foram estimadas e os modelos mais bem ajustados foram selecionados usando o critério de informação de desvio. Resultados: Nas análises de medidas repetidas, as herdabilidades diretas e maternas estimadas e o efeito do ambiente permanente (±SE), de acordo com o modelo mais bem ajustado (modelo 5), foram 0,01 (0,010), 0,02 (0,014) e 0,01 (0,011), respectivamente. Na análise univariada, as melhores estimativas das herdabilidades direta e materna foram 0,12 (0,064) e 0,08 (0,045), respectivamente. Uma tendência crescente para as herdabilidades direta e materna foi observada na paridade 2 (0,15 (0,082) e 0,25 (0,083), respectivamente). Na análise bivariada, as melhores estimativas de herdabilidades direta e materna para LSB foram 0,03 (0,027) e 0,22 (0,041), respectivamente. As correlações genéticas diretas e maternas entre os partos foram 0,25 (0,054) e 0,12 (0,021), respectivamente. Conclusões: Os resultados mostraram uma influência considerável dos fatores ambientais na LSB em cada paridade de ovelhas; também, parâmetros genéticos estatisticamente diferentes (p<0,05) foram obtidos de uma paridade para outra, indicando as diferentes e grandes influências de fatores genéticos e ambientais para cada paridade em ovinos. Os resultados deste estudo podem ser ainda mais definidos usando dados SNPs de todo o genoma em diferentes partes para lidar com uma ampla gama de problemas relacionados à interação do ambiente genético do traço LSB.

Identification of polymorphisms in the oocyte-derived growth differentiation growth factor 9 (GDF9) gene associated with litter size in New Zealand sheep (Ovis aries) breeds.

Having the ability to control litter size is important for sheep farmers and breeders worldwide. However, making genetic gain in key livestock traits like reproductive performance needs typically a lot of time, and both the fecundity and fertility traits have a great economic importance. Attention has therefore turned to better understanding the genes that control reproductive performance. Of these genes, research has focussed on the growth differentiation growth factor 9 (GDF9) gene (GDF9). In this study, a PCR-single strand conformation polymorphism (PCR-SSCP) approach was used to investigate variation in this gene in separate groups of purebred Finnish Landrace sheep, Finnish Landrace × Texel-cross sheep and composite sheep of undefined breed background, but based on New Zealand Romney-type genetics. Three GDF9 variants (named A, B and C) were found, and upon DNA sequencing, the nucleotide substitutions c.978A>G, c.994G>A and c.1111G>A were revealed. The frequency of variant A (containing nucleotides c.978A, c.994G and c.1111G) in the Finnish Landrace, Finnish Landrace × Texel-cross and composite sheep was 0.86, 0.78 and 0.76, respectively. In these three sheep groups, the frequency of B (defined by the presence of nucleotides c.978G and c.994A) was 0.01, 0.03 and 0.23 and for C (containing c.1111A) was 0.13, 0.18 and 0.01, respectively. An animal model was used to estimate the additive effect of fertility data for Finnish Landrace × Texel-cross sheep and revealed an association between litter size and the c.1111G>A variation (p = .036), but this was not observed for the Finnish Landrace sheep (p = .27) or the composite sheep (p = .17). When all the sheep were analysed together, the presence of c.1111A was associated (p < .05) with increased litter size, when compared to ewes that had c.1111G. Litter size did not differ between sheep with and without c.994A in all three groups of sheep investigated. This study suggests that c.1111A could be a useful genetic marker for improving fecundity in New Zealand sheep breeds and that it could be introgressed into other breeds, but analysis of more sheep will be required to confirm the associations that have been observed here.

Associations between the Bovine Myostatin Gene and Milk Fatty Acid Composition in New Zealand Holstein-Friesian × Jersey-Cross Cows.

The myostatin gene (MSTN), which encodes the protein myostatin, is pleiotropic, and its expression has been associated with both increased and decreased adipogenesis and increased skeletal muscle mass in animals. In this study, the polymerase chain reaction, coupled with single strand conformation polymorphism analysis, was utilized to reveal nucleotide sequence variation in bovine MSTN in 410 New Zealand (NZ) Holstein-Friesian × Jersey (HF × J)-cross cows. These cows ranged from 3 to 9 years of age and over the time studied, produced an average 22.53 ± 2.18 L of milk per day, with an average milk fat content of 4.94 ± 0.17% and average milk protein content of 4.03 ± 0.10%. Analysis of a 406-bp amplicon from the intron 1 region, revealed five nucleotide sequence variants (A-E) that contained seven nucleotide substitutions. Using general linear mixed-effect model analyses the AD genotype was associated with reduced C10:0, C12:0, and C12:1 levels when compared to levels in cows with the AA genotype. These associations in NZ HF × J cross cows are novel, and they suggest that this variation in bovine MSTN could be explored for increasing the amount of milk unsaturated fatty acid and decreasing the amount of saturated fatty acid.

A new DNA sequence entropy-based Kullback-Leibler algorithm for gene clustering.

Information theory is a branch of mathematics that overlaps with communications, biology, and medical engineering. Entropy is a measure of uncertainty in the set of information. In this study, for each gene and its exons sets, the entropy was calculated in orders one to four. Based on the relative entropy of genes and exons, Kullback-Leibler divergence was calculated. After obtaining the Kullback-Leibler distance for genes and exons sets, the results were entered as input into 7 clustering algorithms: single, complete, average, weighted, centroid, median, and K-means. To aggregate the results of clustering, the AdaBoost algorithm was used. Finally, the results of the AdaBoost algorithm were investigated by GeneMANIA prediction server to explore the results from gene annotation point of view. All calculations were performed using the MATLAB Engineering Software (2015). Following our findings on investigating the results of genes metabolic pathways based on the gene annotations, it was revealed that our proposed clustering method yielded correct, logical, and fast results. This method at the same that had not had the disadvantages of aligning allowed the genes with actual length and content to be considered and also did not require high memory for large-length sequences. We believe that the performance of the proposed method could be used with other competitive gene clustering methods to group biologically relevant set of genes. Also, the proposed method can be seen as a predictive method for those genes bearing up weak genomic annotations.

Genetic variations and haplotypic diversity in the Myostatin gene of New Zealand cattle breeds.

Myostatin (MSTN) is a circulating factor that is secreted by muscle cells, and that acts upon those cells to inhibit the proliferation of muscle fibres during pre-natal muscle growth. The Polymerase Chain Reaction (PCR) coupled with Single Strand Conformational Polymorphism (SSCP) analysis, was used to reveal variation in the bovine MSTN gene (MSTN) in 722 cattle from a variety of breeds farmed in New Zealand (NZ). These included Hereford, Angus, Charolais, Simmental, Red Poll, South Devon, Shorthorn, Murray Grey, cross-bred Holstein-Friesian × Jersey cattle, and other composite breeds of cattle. Sequence analysis of five regions of MSTN that encompassed coding and non-coding regions of the gene, revealed a total of twelve single-nucleotide substitutions (7 in intron 1 and 5 in a region spanning the intron 2 - exon 3 boundary), and a single nucleotide deletion. Of these 12 substitutions, five are reported here for the first time, whereas seven have been previously described. The deletion c.748-78del, was located in the intron 2 - exon 3 boundary region, and has been reported previously. No nucleotide variation was identified in exons 1, 2 and 3. A total of 18 extended haplotypes were resolved spanning two variable regions (intron 1 and the intron 2 - exon 3 boundary), some of which were common across the breeds, while others were peculiar to particular breeds. The genetic variations identified provide insight into the conserved and polymorphic nature of the coding and non-coding sequences of bovine MSTN respectively, and thus provides a baseline for further study into how variation in the gene might affect growth and carcass traits in NZ cattle.

Effects of genetic polymorphism in Pit1, GH, GHR and KCN3 on milk yield and body weight of Khuzestan (Iran) water buffaloes / Efectos del polimorfismo genético en Pit1, GH, GHR y KCN3 sobre la producción de leche y el peso corporal del búfalo de agua de Juzestán, Irán / Efeitos do polimorfismo genético em Pit1, GH, GHR e KCN3 sobre produção de leite e peso corporal do búfalo de água do Cuzistão, Irã

Abstract Background: Genetic information is necessary to devise strategic plans aimed to improve the genetic merit of buffalos. Objective: To assess the effect of genetic polymorphisms in GH, Pit-1, GHR, GHRHR, and KCN3 genes on milk production and body weight of Khuzestan water buffaloes. Methods: Blood samples were collected from 60 buffaloes from the Khuzestan province, Iran. Using the PCR-RFLP technique, the amplified and digested fragments of GH/AluI, GHR/AluI, GHRHR/ HaeIII, Pit1/HinfI, and KCN3/HindIII were genotyped. Results: All animals were monomorphic for GHRHR. The frequency of mutant alleles for GH, GHR, KCN3, and Pit1 was 47.5, 74.2, 49.2, and 51.7%, respectively. There were significant differences (p<0.0001) in the genotypic frequencies of GH, GHR, and Pit1 between high and low milk-yielding buffaloes. The GH (p=0.0002), GHR (p<0.0001) and Pit1 (p<0.0001) polymorphisms also had significant effects on body weight. Sequencing results revealed the presence of C496A, G495A, G498A and C1501T SNPs in the GH, and G1702T in the GHR gene of Khuzestan buffalos. Conclusion: This study highlights the importance of GH, GHR, and Pit1 on milk production and body weight of Khuzestan buffaloes. The results suggest that devising an integrated breeding plan in Khuzestan water buffalos can considerably benefit from the very high diversity in candidate genes.

Resumen Antecedentes: La información genética es necesaria para diseñar planes estratégicos con el objeto de mejorar el mérito genético de los búfalos. Objetivo: Evaluar el efecto de los polimorfismos genéticos en los genes GH, Pit-1, GHR, GHRHR y KCN3 sobre la producción láctea y peso corporal de búfalos de agua de la provincia de Juzestán, Iran. Métodos: Se recolectaron 60 muestras de sangre de búfalos de la provincia de Juzestán, en Irán. Los fragmentos amplificados y digeridos de GH/AluI, GHR/AluI, GHRHR/HaeIII, Pit1/HinfI y KCN3/HindIII fueron clasificados genotípicamente, utilizando la técnica PCR-RFLP. Resultados: Todos los animales fueron monomórficos para el gen GHRHR. La frecuencia alélica de alelos mutantes para los genes GH, GHR, KCN3 y Pit1 fue 47,5, 74,2, 49,2 y 51,7%, respectivamente. Se encontraron diferencias significativas (p<0,0001) en las frecuencias genotípicas de GH, GHR y Pit1 entre búfalos de alta y baja producción. El efecto del polimorfismo GH (p=0,0002), GHR (p<0,0001) y Pit1 (p<0,0001) también fue significativo para peso corporal. Los resultados de la secuenciación revelaron la presencia de SNPs C496A, G495A, G498A y C1501T en GH, y G1702T en el gen GHR. Conclusiones: Este estudio resalta la importancia de los genes GH, GHR y Pit1 sobre la producción de leche y el peso corporal de búfalos de Juzestán. Los resultados sugieren que la elaboración de un plan de cruzamiento integrado en búfalos de agua de Juzestán puede beneficiarse considerablemente de la gran diversidad de genes candidatos.

Resumo Antecedentes: Determinação informações genéticas é o passo crítico para elaborar planos estratégicos com o objetivo de melhorar o mérito genético dos búfalos. Objetivo: Avaliar o efeito de polimorfismos genéticos nos genes GH, Pit-1, GHR, GHRHR e KCN3 na produção de leite e no peso corporal dos búfalos de água do Cuzistão, Irã. Métodos: Amostras de sangue foram coletadas de 60 búfalos da província de Cuzistão, no Irã. Utilizando a técnica PCR-RFLP, os fragmentos amplificados e digeridos de GH/AluI, GHR/AluI, GHRHR/HaeIII, Pit1/HinfI e KCN3/ HindIII foram genotipados. Resultados: Todos os animais eram monomórficos para o gene GHRHR. A freqüência alélica de alelos mutantes para os genes GH, GHR, KCN3 e Pit1 foi 47,5, 74,2, 49,2 e 51,7%, respectivamente. Uma diferença significativa (p<0,0001) foi encontrada nas freqüências genotípicas de os genes GH, GHR e Pit1 entre búfalos de alta e baixa produção. O efeito do polimorfismo GH (p=0,0002), GHR (p<0,0001) e Pit1 (p<0,0001) também foi significativo para o peso corporal. Os resultados da sequenciação revelaram a presença de SNPs C496A, G495A, G498A e C1501T no GH, e G1702T no gene GHR dos buffalos do Cuzistão. Conclusões: Este estudo destacou a importância da GH, GHR e Pit1 na produção de leite e no peso corporal de buffalos do Cuzistão. Os resultados sugerem que a elaboração de um plano de melhoramiento genético integrado em búfalos de água do Cuzistão pode beneficiar consideravelmente da grande diversidade de genes candidatos.

Gene polymorphisms in PROP1 associated with growth traits in sheep.

The PROP paired-like homeobox 1 (PROP1) gene encodes a protein that regulates growth and development in mammals. Possessing DNA-binding and transcriptional activation abilities, PROP1 is able to control the expression of crucial anterior pituitary hormones including growth hormone, thyroid-stimulating hormone, and prolactin. The objective of this study was to identify genetic variation in ovine PROP1 in 670 New Zealand Romney sheep. Three single nucleotide polymorphisms (SNPs) were detected, two of which located in intron 1 were novel (c.109+40 T>C and c.109+207C>T), whilst the one located in exon 1 (c.45A>G) had been previously reported. These SNPs were arranged into three haplotypic variants - A1, B1 and C1. At each locus, all three genotypes were observed with frequencies in accordance with the Hardy-Weinberg Equilibrium. Association analysis revealed that the variant GG, CC and CC genotypes for c.45A>G, c.109+40 T>C and c.109+207C>T respectively were significantly associated with higher lamb tailing and weaning weights, and growth rate-to-weaning. The A1 haplotype had a positive effect on tailing weight, weaning weight and growth rate, while the B1 haplotype impacted growth traits negatively. These findings suggest that variations in ovine PROP1 could serve as potential genetic markers for use in marker-assisted selection and the breeding for animals with superior growth traits.