Impact of QTL properties on the accuracy of multi-breed genomic prediction

Background

Although simulation studies show that combining multiple breeds in one reference population increases accuracy of genomic prediction, this is not always confirmed in empirical studies. This discrepancy might be due to the assumptions on quantitative trait loci (QTL) properties applied in simulation studies, including number of QTL, spectrum of QTL allele frequencies across breeds, and distribution of allele substitution effects. We investigated the effects of QTL properties and of including a random across- and within-breed animal effect in a genomic best linear unbiased prediction (GBLUP) model on accuracy of multi-breed genomic prediction using genotypes of Holstein-Friesian and Jersey cows.

Methods

Genotypes of three classes of variants obtained from whole-genome sequence data, with moderately low, very low or extremely low average minor allele frequencies (MAF), were imputed in 3000 Holstein-Friesian and 3000 Jersey cows that had real high-density genotypes. Phenotypes of traits controlled by QTL with different properties were simulated by sampling 100 or 1000 QTL from one class of variants and their allele substitution effects either randomly from a gamma distribution, or computed such that each QTL explained the same variance, i.e. rare alleles had a large effect. Genomic breeding values for 1000 selection candidates per breed were estimated using GBLUP modelsincluding a random across- and a within-breed animal effect.

Results

For all three classes of QTL allele frequency spectra, accuracies of genomic prediction were not affected by the addition of 2000 individuals of the other breed to a reference population of the same breed as the selection candidates. Accuracies of both single- and multi-breed genomic prediction decreased as MAF of QTL decreased, especially when rare alleles had a large effect. Accuracies of genomic prediction were similar for the models with and without a random within-breed animal effect, probably because of insufficient power to separate across- and within-breed animal effects.

Conclusions

Accuracy of both single- and multi-breed genomic prediction depends on the properties of the QTL that underlie the trait. As QTL MAF decreased, accuracy decreased, especially when rare alleles had a large effect. This demonstrates that QTL properties are key parameters that determine the accuracy of genomic prediction.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-015-0124-6) contains supplementary material, which is available to authorized users.     

Physical illness in patients with severe mental disorders. II. Barriers to care, monitoring and treatment guidelines, plus recommendations at the system and individual level

Physical disorders are, compared to the general population, more prevalent in people with severe mental illness (SMI). Although this excess morbidity and mortality is largely due to modifiable lifestyle risk factors, the screening and assessment of physical health aspects remains poor, even in developed countries. Moreover, specific patient, provider, treatment and system factors act as barriers to the recognition and to the management of physical diseases in people with SMI. Psychiatrists can play a pivotal role in the improvement of the physical health of these patients by expanding their task from clinical psychiatric care to the monitoring and treatment of crucial physical parameters. At a system level, actions are not easy to realize, especially for developing countries. However, at an individual level, even simple and very basic monitoring and treatment actions, undertaken by the treating clinician, can already improve the problem of suboptimal medical care in this population. Adhering to monitoring and treatment guidelines will result in a substantial enhancement of physical health outcomes. Furthermore, psychiatrists can help educate and motivate people with SMI to address their suboptimal lifestyle, including smoking, unhealthy diet and lack of exercise. The adoption of the recommendations presented in this paper across health care systems throughout the world will contribute to a significant improvement in the medical and related psychiatric health outcomes of patients with SMI.     

Molecular phylogeny of shrimps from the genus Lysmata (Caridea: Hippolytidae): the evolutionary origins of protandric simultaneous hermaphroditism and social monogamy

Shrimps from the genus Lysmata are known because of their wide diversity of lifestyles, mating systems, symbiotic partnerships, and conspicuous coloration. They can occur in crowds (large aggregations), in small groups, or as socially monogamous pairs. Shrimps from this genus are rare, if not unique among crustaceans, because of their unusual sexual system. To date, the sexual system of all species investigated comprises a protandric simultaneous hermaphroditism: shrimps initially mature and reproduce as males and later in life turn into functional simultaneous hermaphrodites. The evolutionary relationships of the species within the genus are unsettled. A molecular phylogeny of the group may shed light on the evolutionary origins of the peculiar sexual and social systems of these shrimps and help resolve standing taxonomic questions long overdue. Using a 647-bp alignment of the 16S rRNA mitochondrial DNA, we examined the phylogenetic relationship of 21 species of shrimps from the genus Lysmata from several biogeographical regions; the Atlantic, Pacific, and Indo-Pacific. The resulting phylogeny indicates that the genus is paraphyletic and includes the genus Exhippolysmata . The constituent species are subdivided into three well supported clades: one group exclusively composed of neotropical species; a second clade comprising the Indo-Pacific and Atlantic symbiotic fish cleaner shrimps; and a third clade including tropical and temperate species from the Atlantic and Pacific. The molecular phylogeny presented here does not support a historical contingency hypothesis, previously proposed to explain the origins of protandric simultaneous hermaphroditism within the genus. Furthermore, the present study shows that monogamous pair-living is restricted to one monophyletic group of shrimps and therefore probably evolved only once.  © 2009 The Linnean Society of London, Biological Journal of the Linnean Society , 2009, 96 , 415–424.     

A holistic high-throughput screening framework for biofuel feedstock assessment that characterises variations in soluble sugars and cell wall composition in <Emphasis Type="Italic">Sorghum bicolor</Emphasis>

Background

A major hindrance to the development of high yielding biofuel feedstocks is the ability to rapidly assess large populations for fermentable sugar yields. Whilst recent advances have outlined methods for the rapid assessment of biomass saccharification efficiency, none take into account the total biomass, or the soluble sugar fraction of the plant. Here we present a holistic high-throughput methodology for assessing sweet Sorghum bicolor feedstocks at 10 days post-anthesis for total fermentable sugar yields including stalk biomass, soluble sugar concentrations, and cell wall saccharification efficiency.

Results

A mathematical method for assessing whole S. bicolor stalks using the fourth internode from the base of the plant proved to be an effective high-throughput strategy for assessing stalk biomass, soluble sugar concentrations, and cell wall composition and allowed calculation of total stalk fermentable sugars. A high-throughput method for measuring soluble sucrose, glucose, and fructose using partial least squares (PLS) modelling of juice Fourier transform infrared (FTIR) spectra was developed. The PLS prediction was shown to be highly accurate with each sugar attaining a coefficient of determination (R ² ) of 0.99 with a root mean squared error of prediction (RMSEP) of 11.93, 5.52, and 3.23 mM for sucrose, glucose, and fructose, respectively, which constitutes an error of <4% in each case. The sugar PLS model correlated well with gas chromatography–mass spectrometry (GC-MS) and brix measures. Similarly, a high-throughput method for predicting enzymatic cell wall digestibility using PLS modelling of FTIR spectra obtained from S. bicolor bagasse was developed. The PLS prediction was shown to be accurate with an R ² of 0.94 and RMSEP of 0.64 μg.mgDW^-1.h^-1.

Conclusions

This methodology has been demonstrated as an efficient and effective way to screen large biofuel feedstock populations for biomass, soluble sugar concentrations, and cell wall digestibility simultaneously allowing a total fermentable yield calculation. It unifies and simplifies previous screening methodologies to produce a holistic assessment of biofuel feedstock potential.

     

Coupling of M3 Acetylcholine Receptor to Gq16 Activates a Natriuretic Peptide Receptor Guanylyl Cyclase

Muscarinic activation of tracheal smooth muscle (TSM) involves a M₃AChR/heterotrimeric-G protein/NPR-GC coupling mechanism. G protein activators Mastoparan (MAS) and Mastoparan-7 stimulated 4- and 10-fold the NPR-GC respectively, being insensitive to PTX and antibodies against Gα_i/o subfamily. Muscarinic and MAS stimulation of NPR-GC was blocked by antibodies against C-terminal of Gα_q16, whose expression was confirmed by RT-PCR. However, synthetic peptides from C-terminal of Gα_q15/16 stimulated the NPR-GC. Coupling of α_q16 to M₃AChR is supported by MAS decreased [³H]QNB binding, being abolished after M₃AChR-4-DAMP-alkylation. Anti-i₃M₃AChR antibodies blocked the muscarinic activation of NPR-GC, and synthetic peptide from i₃M₃AChR (M₃P) was more potent than MAS increasing GTPγ [³⁵S] and decreasing the [³H]QNB activities. Coupling between NPR-GC and Gα_q16 was evaluated by using trypsin-solubilized-fraction from TSM membranes, which displayed a MAS-sensitive-NPR-GC activity, being immunoprecipitated with anti-Gα_q16, also showing an immunoreactive heterotrimeric-G-β -subunit. These data support the existence of a novel transducing cascade, involving Gα_q16β γ coupling M₃AChR to NPR-GC.     

Production of Diamino propionic acid ammonia lyase by a new strain of Salmonella typhimurium PU011

Background  

Seeds of the legume plant Lathyrus sativus, which is grown in arid and semi arid tropical regions, contain Diamino Propionic acid (DAP). DAP is a neurotoxin, which, when consumed, causes a disease called Lathyrism. Lathryrism may manifest as Neurolathyrism or Osteolathyrism, in which the nervous system, and bone formation respectively, are affected. DAP ammonia lyase is produced by a few microorganisms such as Salmonella typhi, Salmonella typhimurium and Pseudomonas, and is capable of detoxifying DAP.     

Genetic variation of Saxifraga paniculata Mill. (Saxifragaceae): molecular evidence for glacial relict endemism in central Europe

Saxifraga paniculata Mill. is an amphi-atlantic species that is widely distributed in the Alps but also occurs with disjunct populations in central Europe. These isolated populations are considered to be glacial relicts. In the study presented here, we analysed the genetic variation within and between populations of Saxifraga paniculata in central Europe to test whether the molecular data give evidence for the supposed relict endemism. We used RAPD analysis and the analysis of molecular variance (AMOVA) technique to investigate 30 populations of Saxifraga paniculata from different locations in central Europe and adjacent geographical areas. In the RAPD analysis, 319 fragments could be amplified of which 91.2% were polymorphic. The percentage of polymorphic bands within populations correlated significantly with population size, indicating a higher level of inbreeding in small populations. AMOVA revealed 43.60% of the variation within populations, only 15.45% between populations within locations, and 40.95% between locations. Genetic distance between locations (Φ_ST) correlated significantly with the geographical distance between locations, giving evidence for geographical isolation. In an UPGMA cluster analysis, based on RAPD data, the populations were grouped together according to their location. The results exhibit a strong genetic differentiation which is obviously due to genetic drift in the isolated populations. Our study therefore gives evidence for glacial relict endemism of Saxifraga paniculata in central Europe.  © 2003 The Linnean Society of London, Biological Journal of the Linnean Society , 2003, 80, 11–21.