Genetic evaluation of age at first calving for Guzerá beef cattle using linear, threshold, and survival Bayesian models

Age at first calving (AFC) is characterized as a censored trait due to missing values provided by recording mistakes and nonoccur-rence or delay in calving communication. In this context, we aimed to compare several statistical methods for genetic evaluation of AFC in Guzerá beef cattle under a Bayesian approach. Seven different methods were used for this purpose. The traditional linear mixed model (LM), which considers only uncensored records; the LM with simulated records (SM), which is based on data augmentation framework; the penalty method, in which a constant of 21 d was added to censored records; the bivariate threshold-linear method considering (TLcens) or not (TLmiss) censored information; and the piecewise Weibull proportional hazards model considering (PWPHcens) or not (PWPH) censored records. Heritability estimates ranged from 0.19 (TLcens) to 0.28 (SM) in non-survival approaches; and 0.40 and 0.46 to PWPH and PWPHcens methods, respectively. In general, breeding values correlations between different methods and the percentage of selected bulls in common indicated reranking, with these correlation ranging from -0.28 (between SM and PWPH) to 0.99 (between TLmiss and LM). The traditional LM, which considers only uncensored records, should be preferred due to its robustness and simplicity. Based on cross-validation analyses, we conclude that the TLmiss could be also a suitable alternative for breeding value prediction, and censored methods did not improve the analysis

Censored Bayesian models for genetic evaluation of age at first calving in Brazilian Brahman cattle

We compared different Bayesian models to handle censored data for genetic parameters estimation of age at first calving (AFC) in Brazilian Brahman cattle. Data from females with AFC above 1825 days of age were assumed to have failed to calve and were considered as censored records. Data including information of 53, 703 cows were analyzed through the following methods: conventional linear model method (LM), which consider only uncensored records; simulation method (SM), in which the data were augmented by drawing random samples from positive truncated normal distributions; penalty method (PM), in which a constant of 21 days was added to censored records; and the bivariate threshold-linear method (TLcens). The LM was the most suited for genetic evaluation of AFC in Brazilian Brahman cattle based on the predictive ability evaluation through cross-validation analysis. The similar results for LM and PM regarding Spearman correlations, and the higher percentages of selected animals in common, indicated that there was not relevant reranking of animals when censored records were used. In summary, the heritability estimates for AFC ranged from 0.09 (TLcens) to 0.20 (LM). Given its poor predictive performance, the SM is not recommended for handling censored records for genetic evaluation of AFC

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Viral replication modes in single-peak fitness landscapes: A dynamical systems analysis

Positive-sense, single-stranded RNA viruses are important pathogens infecting almost all types of organisms. Experimental evidence from distributions of mutations and from viral RNA amplification suggest that these pathogens may follow different RNA replication modes, ranging from the stamping machine replication (SMR) to the geometric replication (GR) mode. Although previous theoretical work has focused on the evolutionary dynamics of RNA viruses amplifying their genomes with different strategies, little is known in terms of the bifurcations and transitions involving the so-called error threshold (mutation-induced dominance of mutants) and lethal mutagenesis (extinction of all sequences due to mutation accumulation and demographic stochasticity). Here we analyze a dynamical system describing the intracellular amplification of viral RNA genomes evolving on a single-peak fitness landscape focusing on three cases considering neutral, deleterious, and lethal mutants. We analytically derive the critical mutation rates causing lethal mutagenesis and error threshold, governed by transcritical bifurcations that depend on parameters α (parameter introducing the mode of replication), replicative fitness of mutants (k1), and on the spontaneous degradation rates of the sequences (ϵ). Our results relate the error catastrophe with lethal mutagenesis in a model with continuous populations of viral genomes. The former case involves dominance of the mutant sequences, while the latter, a deterministic extinction of the viral RNAs during replication due to increased mutation. For the lethal case the critical mutation rate involving lethal mutagenesis is μc=1−ɛ/α. Here, the SMR involves lower critical mutation rates, being the system more robust to lethal mutagenesis replicating closer to the GR mode. This result is also found for the neutral and deleterious cases, but for these later cases lethal mutagenesis can shift to the error threshold once the replication mode surpasses a threshold given by α=ϵ/k1. © 2018 Elsevier Lt

Avaliação genética do tamanho de leitegada em suínos das raças Landrace e Large White

Objetivou-se com este estudo estimar parâmetros genéticos para o número total de leitões nascidos (NTLN), número de leitões nascidos vivos (NLNV) e número de leitões vivos aos cinco dias de idade (NLV5) com modelos de regressão aleatória e averiguar melhor modelagem da variância residual na avaliação das trajetórias genéticas do tamanho da leitegada de fêmeas Landrace e Large White. Os dados utilizados foram provenientes de uma granja de melhoramento genético de suínos e continham 2.388 observações de fêmeas Landrace e 2.325 de Large White. Os modelos de melhor ajuste para o NTLN e NLV5 foram os que consideraram a variância residual homogênea e, para NLNV, o modelo com quatro classes de variâncias residuais foi o mais adequado (BIC). Para Landrace, o efeito materno não foi significativo. O modelo que incluiu o efeito materno e quatro classes de variância residual foi o que apresentou melhor ajuste para NTLN na raça Large White, sendo os modelos sem efeito materno e com variância residual homogênea os mais adequados para NLNV e NLV5. As herdabilidades estimadas variaram de baixas a altas (0,08-0,34; 0,04-0,29 e 0,05-0,21 na raça Landrace e 0,16-0,30; 0,10-0,37 e 0,09-0,32 na Large White, para NTLN, NLNV e NLV5, respectivamente). A alta correlação de posto entre os valores genéticos do NLNV e NLV5 sugere que não há necessidades do controle do NLV5 nesse programa de melhoramento genético. Maiores ganhos podem ser obtidos pela seleção no NLNV de fêmeas primíparas, em função da diminuição do intervalo de gerações

Efeito do extrato aquoso do algodão de seda (Calotropis procera Aiton) sobre a eficiência reprodutiva do carrapato bovino

O carrapato Rhipicephalus microplus é um dos principais parasitos dos rebanhos bovinos. Diferentes grupos de carrapaticidas sintéticos têm sido empregados para o controle desse ácaro, contudo, o uso constante desses produtos tem selecionado populações resistentes. Na tentativa de minimizar esses impactos tem-se buscado avaliar fitoterápicos para o controle desse parasito. Assim, objetivou-se analisar a eficácia in vitro do extrato aquoso do algodão de seda em diferentes concentrações no controle da postura e eclodibilidade dos ovos do R. microplus. Foram avaliados os efeitos das concentrações 1, 5, 10, 25, 50, 75 e 100% do extrato aquoso obtido juntamente com controles com água destilada ou com cipermetrina, 12,5 mg L-1, associada a organofosforado, 150 mg L-1, sobre a eficiência reprodutiva do carrapato. Foi realizado o biocarrapaticidograma sendo que a eficácia acaricida das concentrações 5, 25 e 100% foram superiores àquela observada para o produto comercial utilizado, que correspondeu a 93,98%, indicando a importância de futuras pesquisas para avaliar o potencial toxigênico e a eficácia in vivo dessa planta para o controle do R. microplus

Utilidad de la colonografía por tomografía o colonoscopia virtual

OBJETIVO : revisar los resultados de las colonografías por tomografía (o colonoscopias virtuales) realizadas en nuestro servicio y compararlos con los de la literatura. MATERIAL Y MÉTODO: revisamos las colonoscopias virtuales efectuadas durante 4 años. Todos los pacientes fueron preparados con dieta baja en residuos 72 horas antes de la prueba, marcaje de heces con Gastrografín oral ® e insuflación mecánica del colon con CO 2 . Los estudios se realizaron con un tomógrafo con 64 detectores, con técnica de bajo kilovoltaje. El procesado de imagen se realizó en 3D y 2D con seguimiento con colonoscopia óptica, cirugía de las neoplasias y pólipos detectados, o ambos. RESULTADOS: se llevaron a cabo 750 colonoscopias virtuales, en 410 pacientes fue solicitada tras colonoscopia óptica incom- pleta, en 178 pacientes sintomáticos con contraindicación o riesgo de colonoscopia óptica y 122 de cribado, no pudiendo ser valorables 40 (5%); fueron normales 408 (55%) y fueron pa- tológicas 302 (40%). De las colonoscopias virtuales patológicas en 139 pacientes encontramos procesos neoplásicos y en 13 un proceso neoplásico sincrónico con sensibilidad, especificidad y prevalencia del cáncer colorrectal de 99, 95 y 3.8%, respectiva- mente. Asimismo, se efectuaron seguimientos con colonoscopia óptica y anatomía patológica de 229 pólipos con sensibilidad, especificidad y valor predictivo positivo de 94, 95 y 89%, respec- tivamente; que aumentaron a 100, 99.5 y 97% cuando estudiamos los pólipos ≥ 10 mm. CONCLUSIÓN: la colonoscopia virtual es una exploración útil con indicaciones claras, tras colonoscopias ópticas incompletas de cualquier causa, en pacientes sintomáticos con contraindicaciones o riesgos en la realización de colonoscopias ópticas y en programas de tamizado para cáncer de colon

Genome association study through nonlinear mixed models revealed new candidate genes for pig growth curves

Genome association analyses have been successful in identifying quantitative trait loci (QTLs) for pig body weights measured at a single age. However, when considering the whole weight trajectories over time in the context of genome association analyses, it is important to look at the markers that affect growth curve parameters. The easiest way to consider them is via the two-step method, in which the growth curve parameters and marker effects are estimated separately, thereby resulting in a reduction of the statistical power and the precision of estimates. One efficient solution is to adopt nonlinear mixed models (NMM), which enables a joint modeling of the individual growth curves and marker effects. Our aim was to propose a genome association analysis for growth curves in pigs based on NMM as well as to compare it with the traditional two-step method. In addition, we also aimed to identify the nearest candidate genes related to significant SNP (single nucleotide polymorphism) markers. The NMM presented a higher number of significant SNPs for adult weight (A) and maturity rate (K), and provided a direct way to test SNP significance simultaneously for both the A and K parameters. Furthermore, all significant SNPs from the two-step method were also reported in the NMM analysis. The ontology of the three candidate genes (SH3BGRL2, MAPK14, and MYL9) derived from significant SNPs (simultaneously affecting A and K) allows us to make inferences with regards to their contribution to the pig growth process in the population studied