Bayesian inference in genetic parameter estimation of visual scores in Nellore beef-cattle

The aim of this study was to estimate the components of variance and genetic parameters for the visual scores which constitute the Morphological Evaluation System (MES), such as body structure (S), precocity (P) and musculature (M) in Nellore beef-cattle at the weaning and yearling stages, by using threshold Bayesian models. The information used for this was gleaned from visual scores of 5,407 animals evaluated at the weaning and 2,649 at the yearling stages. The genetic parameters for visual score traits were estimated through two-trait analysis, using the threshold animal model, with Bayesian statistics methodology and MTGSAM (Multiple Trait Gibbs Sampler for Animal Models) threshold software. Heritability estimates for S, P and M were 0.68, 0.65 and 0.62 (at weaning) and 0.44, 0.38 and 0.32 (at the yearling stage), respectively. Heritability estimates for S, P and M were found to be high, and so it is expected that these traits should respond favorably to direct selection. The visual scores evaluated at the weaning and yearling stages might be used in the composition of new selection indexes, as they presented sufficient genetic variability to promote genetic progress in such morphological traits

Study of Peri-Articular Anaesthetic for Replacement of the Knee (SPAARK): study protocol for a patient-blinded, randomised controlled superiority trial of liposomal bupivacaine

Background: Optimising the management of peri-operative pain and recovery following knee replacement has been identified as a patient priority. Current pain relief strategies use opiate-based analgesia; however, up to 50% of patients experience significant side effects. Local anaesthetic incisional infiltration is one alternative. The length of the duration of action is a major limiting factor of current local anaesthetic techniques. Liposomal bupivacaine has been reported to be effective for up to 72 h. This randomised controlled trial will evaluate the clinical and cost effectiveness of liposomal bupivacaine. Methods: SPAARK is a patient-blinded, multi-centre, active comparator, superiority, two-arm, parallel-group randomised controlled trial. Five hundred patients undergoing knee replacement will be recruited and randomised to liposomal bupivacaine plus bupivacaine hydrochloride or bupivacaine hydrochloride alone. The co-primary outcomes are the Quality of Recovery 40 measured at 72 h post-surgery and also cumulative pain measured daily using a 0–10 visual analogue scale for the first 3 days following surgery. Secondary outcomes include cumulative opioid consumption, fitness for discharge, functional outcomes assessed using the Oxford Knee Score and American Knee Society Score, the EuroQol five dimensions instrument and complications. A cost utility analysis is also planned. Discussion: The clinical effectiveness and cost effectiveness of liposomal bupivacaine have yet to be evaluated in the National Health Service, making this trial appropriate and timely. Trial registration: ISRCTN registry, ISRCTN54191675. Registered on 14 November 2017

Genotype by environment interaction in Nelore cattle from five Brazilian states

Records from 75,941 Nelore cattle were used to determine the importance of genotype by environment interaction (GEI) in five Brazilian states. (Co)variance components were estimated by single-trait analysis (with yearling weight, W450, considered to be the same trait in all states) and multiple-trait analysis (with the record from each state considered to be a different trait). The direct heritability estimates for yearling weight were 0.51, 0.39, 0.44, 0.37 and 0.41 in the states of Goiás, Mato Grosso, São Paulo, Mato Grosso do Sul and Minas Gerais, respectively. The across-state genetic correlation estimates between Goiás and Mato Grosso, Goiás and Minas Gerais, São Paulo and Minas Gerais, and Mato Grosso do Sul and Minas Gerais ranged from 0.67 to 0.75. These estimates indicate that GEIs are biologically important. No interactions were observed between Goiás and São Paulo, Goiás and Mato Grosso do Sul, Mato Grosso and São Paulo, Mato Grosso and Mato Grosso do Sul, Mato Grosso and Minas Gerais, or São Paulo and Mato Grosso do Sul (0.82 to 0.97). Comparison of single and multiple-trait analyses showed that selection based on the former was less efficient in the presence of GEI, with substantial losses (up to 10%) during selection

Collagen Type IV-Related Nephropathies in Portugal: Pathogenic COL4A5 Mutations and Clinical Characterization of 22 Families

Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies.info:eu-repo/semantics/publishedVersio

Impact of rare variants in ARHGAP29 to the etiology of oral clefts: role of loss-of-function vs missense variants

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a prevalent, complex congenital malformation. Genome-wide association studies (GWAS) on NSCL/P have consistently identified association for the 1p22 region, in which ARHGAP29 has emerged as the main candidate gene. ARHGAP29 re-sequencing studies in NSCL/P patients have identified rare variants; however, their clinical impact is still unclear. In this study we identified 10 rare variants in ARHGAP29, including five missense, one in-frame deletion, and four loss-of-function (LoF) variants, in a cohort of 188 familial NSCL/P cases. A significant mutational burden was found for LoF (Sequence Kernel Association Test, p = 0.0005) but not for missense variants in ARHGAP29, suggesting that only LoF variants contribute to the etiology of NSCL/P. Penetrance was estimated as 59%, indicating that heterozygous LoF variants in ARHGAP29 confer a moderate risk to NSCL/P. The GWAS hits in IRF6 (rs642961) and 1p22 (rs560426 and rs4147811) do not seem to contribute to the penetrance of the phenotype, based on co-segregation analysis. Our data show that rare variants leading to haploinsufficiency of ARHGAP29 represent an important etiological clefting mechanism, and genetic testing for this gene might be taken into consideration in genetic counseling of familial cases

A high-density transcript linkage map with 1,845 expressed genes positioned by microarray-based Single Feature Polymorphisms (SFP) in Eucalyptus

<p>Abstract</p> <p>Background</p> <p>Technological advances are progressively increasing the application of genomics to a wider array of economically and ecologically important species. High-density maps enriched for transcribed genes facilitate the discovery of connections between genes and phenotypes. We report the construction of a high-density linkage map of expressed genes for the heterozygous genome of <it>Eucalyptus </it>using Single Feature Polymorphism (SFP) markers.</p> <p>Results</p> <p>SFP discovery and mapping was achieved using pseudo-testcross screening and selective mapping to simultaneously optimize linkage mapping and microarray costs. SFP genotyping was carried out by hybridizing complementary RNA prepared from 4.5 year-old trees xylem to an SFP array containing 103,000 25-mer oligonucleotide probes representing 20,726 unigenes derived from a modest size expressed sequence tags collection. An SFP-mapping microarray with 43,777 selected candidate SFP probes representing 15,698 genes was subsequently designed and used to genotype SFPs in a larger subset of the segregating population drawn by selective mapping. A total of 1,845 genes were mapped, with 884 of them ordered with high likelihood support on a framework map anchored to 180 microsatellites with average density of 1.2 cM. Using more probes per unigene increased by two-fold the likelihood of detecting segregating SFPs eventually resulting in more genes mapped. <it>In silico </it>validation showed that 87% of the SFPs map to the expected location on the 4.5X draft sequence of the <it>Eucalyptus grandis </it>genome.</p> <p>Conclusions</p> <p>The <it>Eucalyptus </it>1,845 gene map is the most highly enriched map for transcriptional information for any forest tree species to date. It represents a major improvement on the number of genes previously positioned on <it>Eucalyptus </it>maps and provides an initial glimpse at the gene space for this global tree genome. A general protocol is proposed to build high-density transcript linkage maps in less characterized plant species by SFP genotyping with a concurrent objective of reducing microarray costs. HIgh-density gene-rich maps represent a powerful resource to assist gene discovery endeavors when used in combination with QTL and association mapping and should be especially valuable to assist the assembly of reference genome sequences soon to come for several plant and animal species.</p

Seasonality of Human Leptospirosis in Reunion Island (Indian Ocean) and Its Association with Meteorological Data

Background: Leptospirosis is a disease which occurs worldwide but particularly affects tropical areas. Transmission of the disease is dependent on its excretion by reservoir animals and the presence of moist environment which allows the survival of the bacteria. Methods and Findings: A retrospective study was undertaken to describe seasonal patterns of human leptospirosis cases reported by the Centre National de Re´fe´rences des Leptospiroses (CNRL, Pasteur Institute, Paris) between 1998 and 2008, to determine if there was an association between the occurrence of diagnosed cases and rainfall, temperature and global solar radiation (GSR). Meteorological data were recorded in the town of Saint-Beno?¿t (Me´te´o France ''Beaufonds-Miria'' station), located on the windward (East) coast. Time-series analysis was used to identify the variables that best described and predicted the occurrence of cases of leptospirosis on the island. Six hundred and thirteen cases were reported during the 11-year study period, and 359 cases (58.56%) were diagnosed between February and May. A significant correlation was identified between the number of cases in a given month and the associated cumulated rainfall as well as the mean monthly temperature recorded 2 months prior to diagnosis (r = 0.28 and r = 0.23 respectively). The predictive model includes the number of cases of leptospirosis recorded 1 month prior to diagnosis (b = 0.193), the cumulated monthly rainfall recorded 2 months prior to diagnosis (b = 0.145), the average monthly temperature recorded 0 month prior to diagnosis (b = 3.836), and the average monthly GSR recorded 0 month prior to diagnosis (b =21.293). Conclusions: Leptospirosis has a seasonal distribution in Reunion Island. Meteorological data can be used to predict the occurrence of the disease and our statistical model can help to implement seasonal prevention measures. (Résumé d'auteur