Genomic Evaluation for a Crossbreeding System Implementing Breed-of-Origin for Targeted Markers

The genome in crossbred animals is a mosaic of genomic regions inherited from the different parental breeds. We previously showed that effects of haplotypes strongly associated with crossbred performance are different depending upon from which parental breed they are inherited, however, the majority of the genomic regions are not or only weakly associated with crossbred performance. Therefore, our objective was to develop a model that distinguishes between selected single nucleotide polymorphisms (SNP) strongly associated with crossbred performance and all remaining SNP. For the selected SNP, breed-specific allele effects were fitted whereas for the remaining SNP it was assumed that effects are the same across breeds (SEL-BOA model). We used data from three purebred populations; S, LR, and LW, and the corresponding crossbred population. We selected SNP that explained together either 5 or 10% of the total crossbred genetic variance for average daily gain in each breed of origin. The model was compared to a model where all SNP-alleles were allowed to have different effects for crossbred performance depending upon the breed of origin (BOA model) and to a model where all SNP-alleles had the same effect for crossbred performance across breeds (G model). Across the models, the heritability for crossbred performance was very similar with values of 0.29–0.30. With the SEL-BOA models, in general, the purebred-crossbred genetic correlation (rpc) for the selected SNP was larger than for the non-selected SNP. For breed LR, the rpc for selected SNP and non-selected SNP estimated with the SEL-BOA 5% and SEL-BOA 10% were very different compared to the rpc estimated with the G or BOA model. For breeds S and LW, there was not a big discrepancy for the rpc estimated with the SEL-BOA models and with the G or BOA model. The BOA model calculates more accurate breeding values of purebred animals for crossbred performance than the G model when rpc differs (≈10%) between the G and the BOA model. Superiority of the SEL-BOA model compared to the BOA model was only observed for SEL-BOA 10% and when rpc for the selected and non-selected SNP differed both (≈20%) from the rpc estimated by the G or BOA model

Genomic evaluation considering the mosaic genome of the crossbred pig

In pigs, the breeding goal is to improve performance of crossbred (CB) animals in commercial farms. The best purebred (PB) animals to produce CB animals can be selected based on their genomic estimated breeding value (GEBV) for CB performance. GEBVs are the result of combining estimated effects of single nucleotide polymorphisms (SNPs) with the animal’s genotype. Using CB genomic information allows to estimate SNP allele effects accounting for the CB genetic background. The genome of CB animals is a mosaic of genomic regions inherited from the different parental breeds, therefore, this thesis aimed to investigate whether SNP alleles have different effects depending from which parental breed the allele was inherited and study the impact on GEBV of PB animals for CB performance when breed-specific allele effects were taken into consideration. Firstly, I showed that around 94 % of alleles of three-way CB pigs can be assigned a breed of origin. Knowing this, allowed me to implement a model that accounts for breed-specific effects of all SNP alleles. Using results of this model, I showed that estimated effects and explained variance of SNPs strongly associated with CB performance are different depending upon from which parental breed they were inherited, however, the majority of the genomic regions are not or only weakly associated with CB performance. Therefore, I implemented a new model that allows to estimate breed-specific effects only for alleles of SNPs strongly associated with CB performance, and for the rest of the SNPs assumes that allele effects are the same across breeds. Differences of prediction accuracies between models were generally small. When the estimated genetic correlation between the performance of PB and CB animals per breed of origin differed largely across models, it was better to use models that make a distinction of alleles according to their breed of origin and whether or not they were associated to the trait.</p

The HicA toxin from Burkholderia pseudomallei has a role in persister cell formation

© 2014 The Authors Journal compilation. ©2014 Biochemical Society.This is an open access article that is freely available in ORE or from the publisher's website. Please cite the published version.Published by Portland Press on behalf of the Biochemical SocietyTA (toxin-antitoxin) systems are widely distributed amongst bacteria and are associated with the formation of antibiotic tolerant (persister) cells that may have involvement in chronic and recurrent disease. We show that overexpression of the Burkholderia pseudomallei HicA toxin causes growth arrest and increases the number of persister cells tolerant to ciprofloxacin or ceftazidime. Furthermore, our data show that persistence towards ciprofloxacin or ceftazidime can be differentially modulated depending on the level of induction of HicA expression. Deleting the hicAB locus from B. pseudomallei K96243 significantly reduced persister cell frequencies following exposure to ciprofloxacin, but not ceftazidime. The structure of HicA(H24A) was solved by NMR and forms a dsRBD-like (dsRNA-binding domain-like) fold, composed of a triple-stranded β-sheet, with two helices packed against one face. The surface of the protein is highly positively charged indicative of an RNA-binding protein and His24 and Gly22 were functionality important residues. This is the first study demonstrating a role for the HicAB system in bacterial persistence and the first structure of a HicA protein that has been experimentally characterized.Wellcome Trus

Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer’s disease

Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer’s disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.International Society for Neurochemistry (ISN) and Alexander von Humboldt Foundation (to M.C.D.); Agencia Nacional de Promoción Científica y Tecnológica (PBIT/09 2013, PICT2015-0285 and PICT-2016-4647 to L.M.; PICT-2014-1537 to M.C.D.

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6&nbsp;years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P &lt; 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100&nbsp;years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Genomic evaluation for a crossbreeding system implementing breed-of-origin for targeted markers

The genome in crossbred animals is a mosaic of genomic regions inherited from the different parental breeds. We previously showed that effects of haplotypes strongly associated with crossbred performance are different depending upon from which parental breed they are inherited, however, the majority of the genomic regions are not or only weakly associated with crossbred performance. Therefore, our objective was to develop a model that distinguishes between selected single nucleotide polymorphisms (SNP) strongly associated with crossbred performance and all remaining SNP. For the selected SNP, breed-specific allele effects were fitted whereas for the remaining SNP it was assumed that effects are the same across breeds (SEL-BOA model). We used data from three purebred populations; S, LR, and LW, and the corresponding crossbred population. We selected SNP that explained together either 5 or 10% of the total crossbred genetic variance for average daily gain in each breed of origin. The model was compared to a model where all SNP-alleles were allowed to have different effects for crossbred performance depending upon the breed of origin (BOA model) and to a model where all SNP-alleles had the same effect for crossbred performance across breeds (G model). Across the models, the heritability for crossbred performance was very similar with values of 0.29-0.30. With the SEL-BOA models, in general, the purebred-crossbred genetic correlation (rpc) for the selected SNP was larger than for the non-selected SNP. For breed LR, the rpc for selected SNP and non-selected SNP estimated with the SEL-BOA 5% and SEL-BOA 10% were very different compared to the rpc estimated with the G or BOA model. For breeds S and LW, there was not a big discrepancy for the rpc estimated with the SEL-BOA models and with the G or BOA model. The BOA model calculates more accurate breeding values of purebred animals for crossbred performance than the G model when rpc differs (≈10%) between the G and the BOA model. Superiority of the SEL-BOA model compared to the BOA model was only observed for SEL-BOA 10% and when rpc for the selected and non-selected SNP differed both (≈20%) from the rpc estimated by the G or BOA model.</p