Regression on markers with uncertain allele transmission for QTL mapping in half-sib designs

International audienc

¿Can crossbred animals be used for genomic selection?

Ponencia publicada en ITEA, vol.104La producción en poblaciones “puras” suele tener una baja reproducibilidad en sus descendentes “cruzados”. La selección genómica podría utilizarse para evaluar poblaciones “puras” usando los datos de sus descendientes “cruzados”. Sin embargo, en las poblaciones cruzadas quizás el desequilibrio de ligamiento (LD) no esta restringido a marcadores estrechamente ligados al QTL y los efectos de los marcadores podrían ser específicos de cada población. Estos dos problemas podrían solucionarse utilizando un modelo con los alelos de los SNPs específicos para cada población. Para investigar esta idea usamos un modelo con los efectos de los genotipos de los SNPs (modelo 1) y otro modelo con los efectos de alelos de los SNPs específicos para cada población (modelo 2). Ambos modelos se utilizaron para predecir los valores genéticos de las poblaciones “puras” usando datos F1. Tres situaciones fueron simuladas, en las dos primeras se consideró que las dos poblaciones tenían un mismo origen con una diferencia de 50 y 550 generaciones, respectivamente. En la tercera situación se consideró que las dos poblaciones tenían orígenes distintos. En todos los casos las dos poblaciones generaron una población F1 con un tamaño de 1.000 individuos. Los valores fenotípicos de la F1 fueron simulados con una media de 12 QTL segregando y una heredabilidad de 0.3. En el análisis de la F1 y la población “pura” de validación se escogieron 500 marcadores en segregación. Para estimar el efecto de los SNPs se utilizó el método Bayesiano llamado Bayes-B. La precisión media de los valores genéticos obtenida varió entre 0.789 y 0.718. Sin embargo, se observó que conforme las poblaciones estuvieron más alejadas la precisión disminuyó y el modelo 2 dio valores ligeramente superiores que el modelo 1. Estos resultados sugerirían que los animales cruzados pueden ser utilizados para evaluar poblaciones “puras”. Además modelos con origen específico de población darían mejores resultados.Performance of purebred parents can be a poor predictor of performance of their crossbred descendants. However, in crossbred populations linkage disequilibrium may not be restricted to markers that are tightly linked to the QTL and the effects of SNPs may be breed specific. Both these problems can be addressed by using a model with breed-specific SNP effects. To investigate this idea, we used a model with effects of SNP genotypes (model 1) and a model with breed-specific effects of SNP alleles (model 2) to predict purebred breeding values using F1 data. Three scenarios were considered. In the first two, pure breeds were assumed to have a common origin either 50 or 550 generations ago. In the third scenario, the two breeds did not have a common origin. In all these scenarios, the two breeds were used to generate an F1 with 1,000 individuals. Trait phenotypic values controlled by 12 segregating QTL and with a heritability of 0.30 were simulated for the F1 individuals. Further, 500 segregating markers on a chromosome of 1 Morgan were chosen for analysis in the F1s and in the validation population of purebred. A Bayesian method (Bayes-B) was used to estimate the SNP effects. The accuracy of the predictions was between 0.789 and 0.718. However, the accuracy was lower when the populations were more separate and model 2 gave values slightly higher than model 1. These results suggest that crossbred data could be used to evaluate purebreds and breed specific models could give better results

Nipbl Interacts with Zfp609 and the Integrator Complex to Regulate Cortical Neuron Migration

Mutations in NIPBL are the most frequent cause of Cornelia de Lange syndrome (CdLS), a developmental disorder encompassin

Study protocol: a randomised controlled trial on the clinical effects of levothyroxine treatment for subclinical hypothyroidism in people aged 80 years and over

Background: Subclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base. Methods: The IEMO 80-plus thyroid trial was explicitly designed as an ancillary experiment to the Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism randomised placebo controlled Trial (TRUST) with a near identical protocol and shared research infrastructure. Outcomes will be presented separately for the IEMO and TRUST 80-plus groups, as well as a pre-planned combined analysis of the 145 participants included in the IEMO trial and the 146 participants from the TRUST thyroid trial aged 80 years and over. The IEMO 80-plus thyroid trial is a multi-centre randomised double-blind placebo-controlled parallel group trial of levothyroxine treatment in community-dwelling participants aged 80 years and over with persistent subclinical hypothyroidism (TSH ≥4.6 and ≤ 19.9 mU/L and fT4 within laboratory reference ranges). Participants are randomised to levothyroxine 25 or 50 micrograms daily or matching placebo with dose titrations according to TSH levels, for a minimum follow-up of one and a maximum of three years. Primary study endpoints: hypothyroid physical symptoms and tiredness on the thyroid-related quality of life patient-reported outcome (ThyPRO) at one year. Secondary endpoints: generic quality of life, executive cognitive function, handgrip strength, functional ability, blood pressure, weight, body mass index, and mortality. Adverse events will be recorded with specific interest on cardiovascular endpoints such as atrial fibrillation and heart failure. Discussion: The combined analysis of participants in the IEMO 80-plus thyroid trial with the participants aged over 80 in the TRUST trial will provide the largest experimental evidence base on multimodal effects of levothyroxine treatment in 80-plus persons to date

Predicting urinary creatinine excretion and its usefulness to identify incomplete 24h urine collections

Studies using 24 h urine collections need to incorporate ways to validate the completeness of the urine samples. Models to predict urinary creatinine excretion (UCE) have been developed for this purpose; however, information on their usefulness to identify incomplete urine collections is limited. We aimed to develop a model for predicting UCE and to assess the performance of a creatinine index using para-aminobenzoic acid (PABA) as a reference. Data were taken from the European Food Consumption Validation study comprising two non-consecutive 24 h urine collections from 600 subjects in five European countries. Data from one collection were used to build a multiple linear regression model to predict UCE, and data from the other collection were used for performance testing of a creatinine index-based strategy to identify incomplete collections. Multiple linear regression (n 458) of UCE showed a significant positive association for body weight (ß = 0·07), the interaction term sex × weight (ß = 0·09, reference women) and protein intake (ß = 0·02). A significant negative association was found for age (ß = - 0·09) and sex (ß = - 3·14, reference women). An index of observed-to-predicted creatinine resulted in a sensitivity to identify incomplete collections of 0·06 (95 % CI 0·01, 0·20) and 0·11 (95 % CI 0·03, 0·22) in men and women, respectively. Specificity was 0·97 (95 % CI 0·97, 0·98) in men and 0·98 (95 % CI 0·98, 0·99) in women. The present study shows that UCE can be predicted from weight, age and sex. However, the results revealed that a creatinine index based on these predictions is not sufficiently sensitive to exclude incomplete 24 h urine collections

Genetic parameters and genomic regions associated with piglet response to vaccination for porcine reproductive and respiratory syndrome (PRRS) virus and co-infection with PRRS virus and porcine circovirus type 2b (PCV2b)

Citation: Dunkelberger, J. R., Serao, N. V. L., Kerrigan, M. A., Lunney, J. K., Rowland, R. R. R., & Dekkers, J. C. M. (2016). Genetic parameters and genomic regions associated with piglet response to vaccination for porcine reproductive and respiratory syndrome (PRRS) virus and co-infection with PRRS virus and porcine circovirus type 2b (PCV2b). Journal of Animal Science, 94, 52-53. doi:10.2527/msasas2016-112Objectives of this research were to estimate genetic parameters and to identify genomic regions associated with PRRS viral load (VL), PCV2b VL, and average daily gain (ADG) in nursery pigs vaccinated or non-vaccinated for PRRS virus (PRRSV), followed by co-infection with PRRSV and PCV2b. Data used included 396 commercial crossbred pigs from two PRRS Host Genetics Consortium trials, all from the same genetic supplier. Pigs were sent to Kansas State University after weaning and randomly sorted into two rooms. All pigs in one room were vaccinated for PRRS, and 28 d later, pigs in both rooms were co-infected with PRRSV and PCV2b, followed for 42 d, and genotyped using the 80K BeadChip. PRRS VL after vaccination and post co-infection and PCV2b VL were calculated as area under the curve of serum viremia from ?28 to 0, 0 to 21, and 0 to 42 d post co-infection, respectively. Genetic parameters were estimated by fitting multivariate animal models in ASReml4 with litter and pen (trial) as additional random effects. Trait-specific fixed effects of trial and weight and age at vaccination were also fitted. Genome-wide association (GWA) studies were performed by fitting SNPs as fixed effects one at a time in bivariate animal models for the non-vaccinated (Non-Vx) and vaccinated (Vx) groups for each trait. Heritability estimates following vaccination were 0.31, 0.07, and 0.10 for ADG Non-Vx, ADG Vx, and PRRS Vx, respectively. During the co-infection period, heritability estimates were slightly higher at 0.53, 0.57, 0.56, 0.20, 0.18, and 0.15 for ADG Non-Vx, ADG Vx, PRRS Non-Vx, PRRS Vx, PCV2b Non-Vx, and PCV2b Vx, respectively. Standard errors ranged from 0.14 to 0.22. A strong, positive genetic correlation (0.95 ± 1.01) was observed for PRRS VL post-vaccination with PRRS VL Non-Vx. Unique genomic regions were identified between Vx and Non-Vx pigs for each trait, the most significant of which was identified for PCV2b VL and located near the major histocompatibility complex, an important region for response to infection. The chromosome 4 region, which has been associated with VL following PRRSV-only infection, was associated with PRRS VL Non-Vx but not PRRS Vx or PRRS VL post-vaccination. Together, these results suggest that selection for improved performance under co-infection of PRRS and PCV2b is possible. Additionally, identification of unique genomic regions between Vx and Non-Vx pigs may enable selection of pigs with better response to vaccination. This research was supported by USDA-NIFA grants 2012–38420–19286 and 2013–68004–20362