A bayesian model for the analysis of transgenerational epigenetic variation

477-485Epigenetics has become one of the major areas of biological research. However, the degree of phenotypic variability that is explained by epigenetic processes still remains unclear. From a quantitative genetics perspective, the estimation of variance components is achieved by means of the information provided by the resemblance between relatives. In a previous study, this resemblance was described as a function of the epigenetic variance component and a reset coefficient that indicates the rate of dissipation of epigenetic marks across generations. Given these assumptions, we propose a Bayesian mixed model methodology that allows the estimation of epigenetic variance from a genealogical and phenotypic database. The methodology is based on the development of a T matrix of epigenetic relationships that depends on the reset coefficient. In addition, we present a simple procedure for the calculation of the inverse of this matrix (T-1) and a Gibbs sampler algorithm that obtains posterior estimates of all the unknowns in the model. The new procedure was used with two simulated data sets and with a beef cattle database. In the simulated populations, the results of the analysis provided marginal posterior distributions that included the population parameters in the regions of highest posterior density. In the case of the beef cattle dataset, the posterior estimate of transgenerational epigenetic variability was very low and a model comparison test indicated that a model that did not included it was the most plausible

Linkage disequilibrium, persistence of phase, and effective population size in Spanish local beef cattle breeds assessed through a high-density single nucleotide polymorphism chip

We have used the BovineHD Genotyping BeadChip to obtain high density genotypes (>700, 000 SNP after quality control) from 116 trios in five Spanish local beef cattle breeds. Linkage disequilibrium (LD) was meas- ured through the r2 statistic. Average r2 for adjacent markers in the five breeds were very close, around 0.52, and de- creased with increasing distance between markers, although in long distances some LD remained (0.07 and 0.05 for markers 200 kb and 1000 kb apart, respectively). At all distances the standard deviations were large and the shape of the distribution varied depending upon the marker dis- tance. Average r2 varied also between chromosomes. Pair- wise correlations between the r’s estimated in two breeds at short distances (5 kb) was in the rank of 0.6 – 0.7. Similarly to r2 estimates, this correlation decreased with increasing marker distance

Detección de regiones genómicas con elevado desequilibrio de ligamiento en poblaciones de vacuno de carne españolas con análisis de BovineHD BeadChip

Mouresan, E. F. Universidad de Zaragoza. Facultad de Veterinaria. Unidad de Mejora Genética. Zaragoza, España.González Rodríguez, A. Universidad de Zaragoza. Facultad de Veterinaria. Unidad de Mejora Genética. Zaragoza, España.Munilla, Sebastián. Universidad de Zaragoza. Facultad de Veterinaria. Unidad de Mejora Genética. Zaragoza, España.Moreno, C. Universidad de Zaragoza. Facultad de Veterinaria. Unidad de Mejora Genética. Zaragoza, España.Altarriba, J. Universidad de Zaragoza. Facultad de Veterinaria. Unidad de Mejora Genética. Zaragoza, España.Díaz, C. Instituto Nacional de Tecnología Agraria y Alimentaria (INIA). Mejora Genética Animal. Madrid, España.Baro, J. A. Universidad de Valladolid. Departamento de Ciencias Agroforestales. Producción Animal. Valladolid. España.Piedrafita, J. Universitad Autónoma de Barcelona. Ciencia Animal y de los Alimentos. Barcelona, España.Molina, A. Universidad de Córdoba. Departamento de Genética. Córdoba. Spain.Cañas Alvarez, J. J. Universitad Autónoma de Barcelona. Ciencia Animal y de los Alimentos. Barcelona, España.Varona, L. Universidad de Zaragoza. Facultad de Veterinaria. Unidad de Mejora Genética. Zaragoza, España.59-65El objetivo de este trabajo fue evaluar el patrón de desequilibrio de ligamiento a lo largo del genoma en siete poblaciones españolas autóctonas de vacuno de carne (Asturiana de los Valles, Avileña Negra - Ibérica, Bruna dels Pirineus, Morucha, Pirenaica, Retinta y Rubia Gallega). Para ello, se utilizó el BovineHD BeadChip con el que se genotiparon 171 tríos formados por individuo/padre/madre. Después del filtrado, se dispuso de 573.134 SNP. A partir de esta información se definió un parámetro que mide el desequilibrio medio del genoma por regiones de 1Mb en cada una de las poblaciones. Los resultados mostraron que el desequilibrio de ligamiento es muy heterogéneo a lo largo del genoma y que, además, esta heterogeneidad es consistente entre poblaciones. Las causas de esta heterogeneidad pueden ser, o bien estructurales y atribuibles a una menor tasa de mutación y/o recombinación, o bien consecuencia de procesos de selección estabilizadora

Detección de regiones genómicas con elevado desequilibrio de ligamiento en poblaciones de vacuno de carne españolas con análisis de BovineHD BeadChip

Mouresan, E. F. Universidad de Zaragoza. Facultad de Veterinaria. Unidad de Mejora Genética. Zaragoza, España.González Rodríguez, A. Universidad de Zaragoza. Facultad de Veterinaria. Unidad de Mejora Genética. Zaragoza, España.Munilla, Sebastián. Universidad de Zaragoza. Facultad de Veterinaria. Unidad de Mejora Genética. Zaragoza, España.Moreno, C. Universidad de Zaragoza. Facultad de Veterinaria. Unidad de Mejora Genética. Zaragoza, España.Altarriba, J. Universidad de Zaragoza. Facultad de Veterinaria. Unidad de Mejora Genética. Zaragoza, España.Díaz, C. Instituto Nacional de Tecnología Agraria y Alimentaria (INIA). Mejora Genética Animal. Madrid, España.Baro, J. A. Universidad de Valladolid. Departamento de Ciencias Agroforestales. Producción Animal. Valladolid. España.Piedrafita, J. Universitad Autónoma de Barcelona. Ciencia Animal y de los Alimentos. Barcelona, España.Molina, A. Universidad de Córdoba. Departamento de Genética. Córdoba. Spain.Cañas Alvarez, J. J. Universitad Autónoma de Barcelona. Ciencia Animal y de los Alimentos. Barcelona, España.Varona, L. Universidad de Zaragoza. Facultad de Veterinaria. Unidad de Mejora Genética. Zaragoza, España.59-65El objetivo de este trabajo fue evaluar el patrón de desequilibrio de ligamiento a lo largo del genoma en siete poblaciones españolas autóctonas de vacuno de carne (Asturiana de los Valles, Avileña Negra - Ibérica, Bruna dels Pirineus, Morucha, Pirenaica, Retinta y Rubia Gallega). Para ello, se utilizó el BovineHD BeadChip con el que se genotiparon 171 tríos formados por individuo/padre/madre. Después del filtrado, se dispuso de 573.134 SNP. A partir de esta información se definió un parámetro que mide el desequilibrio medio del genoma por regiones de 1Mb en cada una de las poblaciones. Los resultados mostraron que el desequilibrio de ligamiento es muy heterogéneo a lo largo del genoma y que, además, esta heterogeneidad es consistente entre poblaciones. Las causas de esta heterogeneidad pueden ser, o bien estructurales y atribuibles a una menor tasa de mutación y/o recombinación, o bien consecuencia de procesos de selección estabilizadora

Proportion and characteristics of secondary progressive multiple sclerosis in five European registries using objective classifiers

Background: To assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing-remitting MS (RRMS) and SPMS and may identify situations where SPMS is under reported.Materials and methods: Data were obtained for 61,900 MS patients from MS registries in the Czech Republic, Denmark, Germany, Sweden, and the United Kingdom (UK), including date of birth, sex, SP conversion year, visits with an Expanded Disability Status Scale (EDSS) score, MS onset and diagnosis date, relapses, and disease-modifying treatment (DMT) use. We included RRMS or SPMS patients with at least one visit between January 2017 and December 2019 if ≥ 18 years of age. We applied three objective methods: A set of SPMS clinical trial inclusion criteria ("EXPAND criteria") modified for a real-world evidence setting, a modified version of the MSBase algorithm, and a decision tree-based algorithm recently published.Results: The clinically assigned proportion of SPMS varied from 8.7% (Czechia) to 34.3% (UK). Objective classifiers estimated the proportion of SPMS from 15.1% (Germany by the EXPAND criteria) to 58.0% (UK by the decision tree method). Due to different requirements of number of EDSS scores, classifiers varied in the proportion they were able to classify; from 18% (UK by the MSBase algorithm) to 100% (the decision tree algorithm for all registries). Objectively classified SPMS patients were older, converted to SPMS later, had higher EDSS at index date and higher EDSS at conversion. More objectively classified SPMS were on DMTs compared to the clinically assigned.Conclusion: SPMS appears to be systematically underdiagnosed in MS registries. Reclassified patients were more commonly on DMTs.</p

Performance of genomic selection under a single-step approach in autochthonous Spanish beef cattle populations

This study evaluated different strategies for implementing a single-step genomic selection programme in two autochthonous Spanish beef cattle populations (Pirenaica—Pi and Rubia Gallega—RG). The strategies were compared in terms of accuracy attained under different scenarios by simulating genomic data over the known genealogy. Several genotyping approaches were tested, as well as, other factors like marker density, effective population size, mutation rate and heritability of the trait. The results obtained showed gains in accuracy with respect to pedigree BLUP evaluation in all cases. The greatest benefit was obtained when the candidates to selection had their genotypes included in the evaluation. Moreover, genotyping the individuals with the most accurate predictions maximized the gains but other suboptimal strategies also yielded satisfactory results. Furthermore, the gains in accuracy increased with the marker density reaching a plateau at around 50,000 markers. Likewise, the effective population size and the mutation rate have also shown an effect, both increasing the accuracy with decreasing values of these population parameters. Finally, the results obtained for the RG population showed greater gains compared to the Pi population, probably attributed to the wider implantation of artificial insemination.Fil: Mouresan, E.-F.. Universidad de Zaragoza; EspañaFil: Altarriba, J.. Universidad de Zaragoza; EspañaFil: Moreno, C.. Universidad de Zaragoza; EspañaFil: Munilla Leguizamon, Sebastian. Universidad de Zaragoza; España. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: González-Rodríguez, A.. Universidad de Zaragoza; EspañaFil: Varona, Luisina. Universidad de Zaragoza; Españ

Genomic differentiation between Asturiana de los Valles, Avileña-Negra Ibérica, Bruna dels Pirineus, Morucha, Pirenaica, Retinta and Rubia Gallega cattle breeds

The Spanish local beef cattle breeds have most likely common origin followed by a process of differentiation. This particular historical evolution has most probably left detectable signatures in the genome. The objective of this study was to identify genomic regions associated with differentiation processes in seven Spanish autochthonous populations (Asturiana de los Valles (AV), Avileña-Negra Ibérica (ANI), Bruna dels Pirineus (BP), Morucha (Mo), Pirenaica (Pi), Retinta (Re) and Rubia Gallega (RG)). The BovineHD 777K BeadChip was used on 342 individuals (AV, n=50; ANI, n=48; BP, n=50; Mo, n=50; Pi, n=48; Re, n=48; RG, n=48) chosen to be as unrelated as possible. We calculated the fixation index (F ST) and performed a Bayesian analysis named SelEstim. The output of both procedures was very similar, although the Bayesian analysis provided a richer inference and allowed us to calculate significance thresholds by generating a pseudo-observed data set from the estimated posterior distributions. We identified a very large number of genomic regions, but when a very restrictive significance threshold was applied these regions were reduced to only 10. Among them, four regions can be highlighted because they comprised a large number of single nucleotide polymorphisms and showed extremely high signals (Kullback-Leiber divergence (KLD)>6). They are located in BTA 2 (5 575 950 to 10 152 228 base pairs (bp)), BTA 5 (17 596 734 to 18 850 702 bp), BTA 6 (37 853 912 to 39 441 548 bp) and BTA 18 (13 345 515 to 15 243 838 bp) and harbor, among others, the MSTN (Myostatin), KIT-LG (KIT Ligand), LAP3 (leucine aminopeptidase 3), NAPCG (non-SMC condensing I complex, subunit G), LCORL (ligand dependent nuclear receptor corepressor-like) and MC1R (Melanocortin 1 receptor) genes. Knowledge on these genomic regions allows to identify potential targets of recent selection and helps to define potential candidate genes associated with traits of interest, such as coat color, muscle development, fertility, growth, carcass and immunological response. © 2017 The Animal Consortium

Evaluation of the potential use of a meta-population for genomic selection in autochthonous beef cattle populations

This study investigated the potential application of genomic selection under a multi-breed scheme in the Spanish autochthonous beef cattle populations using a simulation study that replicates the structure of linkage disequilibrium obtained from a sample of 25 triplets of sire/dam/offspring per population and using the BovineHD Beadchip. Purebred and combined reference sets were used for the genomic evaluation and several scenarios of different genetic architecture of the trait were investigated. The single-breed evaluations yielded the highest within-breed accuracies. Across breed accuracies were found low but positive on average confirming the genetic connectedness between the populations. If the same genotyping effort is split in several populations, the accuracies were lower when compared with single-breed evaluation, but showed a small advantage over small-sized purebred reference sets over the accuracies of subsequent generations. Besides, the genetic architecture of the trait did not show any relevant effect on the accuracy with the exception of rare variants, which yielded slightly lower results and higher loss of predictive ability over the generations.Fil: Mouresan, E. F.. Universidad de Zaragoza; EspañaFil: Cañas Álvarez, J. J.. Universitat Autònoma de Barcelona; EspañaFil: González Rodríguez, A.. Universidad de Zaragoza; EspañaFil: Munilla Leguizamon, Sebastian. Universidad de Zaragoza; España. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Altarriba, J.. Universidad de Zaragoza; España. Instituto Agroalimentario de Aragón; EspañaFil: Díaz, C.. Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria; EspañaFil: Baró, J. A.. Universidad de Valladolid; EspañaFil: Molina, A.. Universidad de Córdoba; EspañaFil: Piedrafita, J.. Universitat Autònoma de Barcelona; EspañaFil: Varona, Luisina. Universidad de Zaragoza; Españ