Design of reference populations for genomic selection in crossbreeding programs

Background

In crossbreeding programs, genomic selection offers the opportunity to make efficient use of information on crossbred (CB) individuals in the selection of purebred (PB) candidates. In such programs, reference populations often contain genotyped PB animals, although the breeding objective is usually more focused on CB performance. The question is what would be the benefit of including a larger proportion of CB individuals in the reference population.

Methods

In a deterministic simulation study, we evaluated the benefit of including various proportions of CB animals in a reference population for genomic selection of PB animals in a crossbreeding program. We used a pig breeding scheme with selection for a moderately heritable trait and a size of 6000 for the reference population.

Results

Applying genomic selection to improve the performance of CB individuals, with a genetic correlation between PB and CB performance (r_PC) of 0.7, selection accuracy of PB candidates increased from 0.49 to 0.52 if the reference population consisted of PB individuals, it increased to 0.55 if the reference population consisted of the same number of CB individuals, and to 0.60 if the size of the CB reference population was twice that of the reference population for each PB line. The advantage of using CB rather than PB individuals increased linearly with the proportion of CB individuals in the reference population. This advantage disappeared quickly if r_PC was higher or if the breeding objective put some emphasis on PB performance. The benefit of adding CB individuals to an existing PB reference population was limited for high r_PC.

Conclusions

Using CB rather than PB individuals in a reference population for genomic selection can provide substantial advantages, but only when correlations between PB and CB performances are not high and PB performance is not part of the breeding objective.     

The sepsis model: an emerging hypothesis for the lethality of inhalation anthrax

Inhalation anthrax is often described as a toxin‐mediated disease. However, the toxaemia model does not account for the high mortality of inhalation anthrax relative to other forms of the disease or for the pathology present in inhalation anthrax. Patients with inhalation anthrax consistently show extreme bacteraemia and, in contrast to animals challenged with toxin, signs of sepsis. Rather than toxaemia, we propose that death in inhalation anthrax results from an overwhelming bacteraemia that leads to severe sepsis. According to our model, the central role of anthrax toxin is to permit the vegetative bacteria to escape immune detection. Other forms of B. anthracis infection have lower mortality because their overt symptoms early in the course of disease cause patients to seek medical care at a time when the infection and its sequelae can still be reversed by antibiotics. Thus, the sepsis model explains key features of inhalation anthrax and may offer a more complete understanding of disease pathology for researchers as well as those involved in the care of patients.     

The genus Gymnospermium (Berberidaceae) in Italy: identity and relationships of the populations at the western limit of the genus range

Abstract

Gymnospermium is a small genus of 7–12 taxa subject to diverging taxonomic treatments and distributed from east China to the Balkans. The recent discovery of Gymnospermium in the S-Apennines posed questions about origin and identity. Accordingly, we performed a systematic investigation by means of morphological, karyological and molecular tools. All populations were diploid with 2n = 14 as for the Balkan G. scipetarum (incl. G. maloi), and also morphology suggested a close affinity to the latter. However, the Italian populations differed from typical G. scipetarum by the lower stamen:petal length and style:carpel length. By including all European and most Asian taxa in a phylogenetic analysis, we shed new light into the species-level relationships in this genus. In the combined ITS-trnL-F phylogeny, two major clades were retrieved. One included the central Asian and eastern European taxa plus the Greek endemic G. peloponnesiacum sister to G. odessanum, and one the Balkan and Apennine populations. Such findings further corroborated that the Apennine plant belong to G. scipetarum. The native status of the Italian population is supported by exclusive SNPs in both ITS1 and trnL-F sequences. Along with morphological evidence, this allows to refer it to the new subspecies G. scipetarum subsp. eddae.     

On the identity of a Centaurea population on Procida Island,Italy: Centaurea corensis rediscovered

The discovery on the Island Procida (Gulf of Naples, off the Italian west coast) of a Centaurea population similar to C. corensis, a narrow-range Sardinian endemic hitherto known only from one single locality in Sardinia, is presented here. The identification of the two populations as C. corensis is confirmed by morphological comparison and morphometric analysis, chromosome counts and nuclear ribosomal DNA sequence data. A recent origin of the species through polyploidization is hypothesized. Finally, the possibility that recent anthropogenic dispersal may account for the disjunction is discussed.     

Mouse Complete Stasis Model of Inferior Vena Cava Thrombosis

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). In the United States (U.S.), the high morbidity and mortality rates make VTE a serious health concern ^1-2. After heart disease and stroke, VTE is the third most common vascular disease ³. In the U.S. alone, there is an estimated 900,000 people affected each year, with 300,000 deaths occurring annually ³. A reliable in vivo animal model to study the mechanisms of this disease is necessary.The advantages of using the mouse complete stasis model of inferior vena cava thrombosis are several. The mouse model allows for the administration of very small volumes of limited availability test agents, reducing costs dramatically. Most promising is the potential for mice with gene knockouts that allow specific inflammatory and coagulation factor functions to be delineated. Current molecular assays allow for the quantitation of vein wall, thrombus, whole blood, and plasma for assays. However, a major concern involving this model is the operative size constraints and the friability of the vessels. Also, due to the small IVC sample weight (mean 0.005 grams) it is necessary to increase animal numbers for accurate statistical analysis for tissue, thrombus, and blood assays such as real-time polymerase chain reaction (RT-PCR), western blot, enzyme-linked immunosorbent (ELISA), zymography, vein wall and thrombus cellular analysis, and whole blood and plasma assays ^4-8.The major disadvantage with the stasis model is that the lack of blood flow inhibits the maximal effect of administered systemic therapeutic agents on the thrombus and vein wall.     

Fyn-Dependent Gene Networks in Acute Ethanol Sensitivity

Studies in humans and animal models document that acute behavioral responses to ethanol are predisposing factor for the risk of long-term drinking behavior. Prior microarray data from our laboratory document strain- and brain region-specific variation in gene expression profile responses to acute ethanol that may be underlying regulators of ethanol behavioral phenotypes. The non-receptor tyrosine kinase Fyn has previously been mechanistically implicated in the sedative-hypnotic response to acute ethanol. To further understand how Fyn may modulate ethanol behaviors, we used whole-genome expression profiling. We characterized basal and acute ethanol-evoked (3 g/kg) gene expression patterns in nucleus accumbens (NAC), prefrontal cortex (PFC), and ventral midbrain (VMB) of control and Fyn knockout mice. Bioinformatics analysis identified a set of Fyn-related gene networks differently regulated by acute ethanol across the three brain regions. In particular, our analysis suggested a coordinate basal decrease in myelin-associated gene expression within NAC and PFC as an underlying factor in sensitivity of Fyn null animals to ethanol sedation. An in silico analysis across the BXD recombinant inbred (RI) strains of mice identified a significant correlation between Fyn expression and a previously published ethanol loss-of-righting-reflex (LORR) phenotype. By combining PFC gene expression correlates to Fyn and LORR across multiple genomic datasets, we identified robust Fyn-centric gene networks related to LORR. Our results thus suggest that multiple system-wide changes exist within specific brain regions of Fyn knockout mice, and that distinct Fyn-dependent expression networks within PFC may be important determinates of the LORR due to acute ethanol. These results add to the interpretation of acute ethanol behavioral sensitivity in Fyn kinase null animals, and identify Fyn-centric gene networks influencing variance in ethanol LORR. Such networks may also inform future design of pharmacotherapies for the treatment and prevention of alcohol use disorders.     

Prevention of lymphocyte apoptosis in septic mice with cancer increases mortality

Lymphocyte apoptosis is thought to have a major role in the pathophysiology of sepsis. However, there is a disconnect between animal models of sepsis and patients with the disease, because the former use subjects that were healthy prior to the onset of infection while most patients have underlying comorbidities. The purpose of this study was to determine whether lymphocyte apoptosis prevention is effective in preventing mortality in septic mice with preexisting cancer. Mice with lymphocyte Bcl-2 overexpression (Bcl-2-Ig) and wild type (WT) mice were injected with a transplantable pancreatic adenocarcinoma cell line. Three weeks later, after development of palpable tumors, all animals received an intratracheal injection of Pseudomonas aeruginosa. Despite having decreased sepsis-induced T and B lymphocyte apoptosis, Bcl-2-Ig mice had markedly increased mortality compared with WT mice following P. aeruginosa pneumonia (85 versus 44% 7-d mortality; p = 0.004). The worsened survival in Bcl-2-Ig mice was associated with increases in Th1 cytokines TNF-α and IFN-γ in bronchoalveolar lavage fluid and decreased production of the Th2 cytokine IL-10 in stimulated splenocytes. There were no differences in tumor size or pulmonary pathology between Bcl-2-Ig and WT mice. To verify that the mortality difference was not specific to Bcl-2 overexpression, similar experiments were performed in Bim(-/-) mice. Septic Bim(-/-) mice with cancer also had increased mortality compared with septic WT mice with cancer. These data demonstrate that, despite overwhelming evidence that prevention of lymphocyte apoptosis is beneficial in septic hosts without comorbidities, the same strategy worsens survival in mice with cancer that are given pneumonia.     

Differential Habitat Use and Niche Partitioning by <Emphasis Type="Italic">Pseudomonas</Emphasis> Species in Human Homes

Many species of Pseudomonas have the ability to use a variety of resources and habitats, and as a result Pseudomonas are often characterized as having broad fundamental niches. We questioned whether actual habitat use by Pseudomonas species is equally broad. To do this, we sampled extensively to describe the biogeography of Pseudomonas within the human home, which presents a wide variety of habitats for microbes that live in close proximity to humans but are not part of the human flora, and for microbes that are opportunistic pathogens, such as Pseudomonas aeruginosa. From 960 samples taken in 20 homes, we obtained 163 Pseudomonas isolates. The most prevalent based on identification using the SepsiTest BLAST analysis of 16S rRNA () were Pseudomonas monteilii (42 isolates), Pseudomonas plecoglossicida, Pseudomonas fulva, and P. aeruginosa (approximately 25 each). Of these, all but P. fulva differed in recovery rates among evaluated habitat types (drains, soils, water, internal vertebrate sites, vertebrate skin, inanimate surfaces, and garbage/compost) and all four species also differed in recovery rates among subcategories of habitat types (e.g., types of soils or drains). We also found that at both levels of habitat resolution, each of these six most common species (the four above plus Pseudomonas putida and Pseudomonas oryzihabitans) were over- or under-represented in some habitats relative to their contributions to the total Pseudomonas collected across all habitats. This pattern is consistent with niche partitioning. These results suggest that, whereas Pseudomonas are often characterized as generalists with broad fundamental niches, these species in fact have more restricted realized niches. Furthermore, niche partitioning driven by competition among Pseudomonas species may be contributing to the observed variability in habitat use by Pseudomonas in this system.