Accuracy of Genomic Prediction when Accounting for Population Structure and Polygenic Effects

Accuracy of genomic estimated breeding values obtained using the standard marker effect model was compared with models that account for population structure, either by applying a transmission disequilibrium test (TDT) approach or by fitting polygenic effects. The TDT approach was inferior to the standard model, whereas fitting polygenic effects in addition to marker effects increased the accuracy of estimated breeding values of the progeny of training individuals but also seven generations after training. Thus, fitting polygenic effects enhances utilization of genomic information both in the short and long-term

Sodium-glucose cotransporter 2 inhibitors:extending the indication to non-diabetic kidney disease?

This year the medical community was pleasantly surprised by the results of the first large outcome trial that primarily examined the renal effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (CANA) in subjects with diabetes and impaired kidney function. The Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE) trial showed that CANA, relative to placebo, reduces the risk for end-stage renal disease, doubling of creatinine or renal death by 34% [hazard ratio 0.66 (95% confidence interval 0.53-0.81]. These effects were consistent across baseline estimated glomerular filtration rate (eGFR) and haemoglobin A1c subgroups. In this review we combine the results of the CREDENCE trial with those of several cardiovascular outcome trials with SGLT2 inhibitors and show that, unexpectedly, patients with lower eGFR levels may have greater benefit with respect to cardiovascular outcome than patients with normal kidney function. The cardio- and renoprotective effects of SGLT2 inhibitors seem to be independent of their glucose-lowering effects, as shown in several post hoc analyses. In this review we discuss the alleged mechanisms of action that explain the beneficial effects of this novel class of drugs. Moreover, we discuss whether these findings indicate that this class of drugs may also be beneficial in non-diabetic chronic kidney diseases

Bayesian Methods for Genomic Prediction and Genome-Wide Association Studies combining Information on Genotyped and Non-Genotyped Individuals

Genomic prediction involves using high-density marker genotypes to characterize the impact on performance of every region of the genome, and using that information to predict performance of genotyped selection candidates. This is a relatively new technology and is now gaining traction in personalized medicine and in various livestock industries. Our new approach promises to overcome serious limitations with existing techniques for genomic prediction

New Diabetes Therapies and Diabetic Kidney Disease Progression:the Role of SGLT-2 Inhibitors

Purpose of Review Sodium-glucose co-transporter 2 (SGLT-2) inhibitors have emerged as a promising drug class for the treatment of diabetic kidney disease. Developed originally as glucose-lowering drugs by enhancing urinary glucose excretion, these drugs also lower many other renal and cardiovascular risk factors such as body weight, blood pressure, albuminuria, and uric acid. Results from the EMPA-REG OUTCOME and CANVAS trials show that these salutary effects translate into a reduction in cardiovascular outcomes and have the potential to delay the progression of kidney function decline. This review summarizes recent studies on the mechanisms and rationale of renoprotective effects. Recent Findings Effects of SGLT-2 inhibitors on the kidney are likely explained by multiple pathways. SGLT-2 inhibitors may improve renal oxygenation and intra-renal inflammation thereby slowing the progression of kidney function decline. Additionally, SGLT-2 inhibitors are associated with a reduction in glomerular hyperfiltration, an effect which is mediated through increased natriuresis and tubuloglomerular feedback and independent of glycemic control. Analogous to diabetic kidney disease, various etiologies of non-diabetic kidney disease are also characterized by single nephron hyperfiltration and elevated albuminuria. This offers the opportunity to reposition SGLT-2 inhibitors from diabetic to non-diabetic kidney disease. Clinical trials are currently ongoing to characterize the efficacy and safety of SGLT-2 inhibitors in patients with diabetic and non-diabetic kidney disease. Summary The glucose-independent hemodynamic mechanisms of SGLT-2 inhibitors provide the possibility to extend the use of SGLT-2 inhibitors to non-diabetic kidney disease. Ongoing dedicated trials have the potential to change clinical practice and outlook of high-risk patients with diabetic (and non-diabetic) kidney disease

A Nested Mixture Model for Genomic Prediction Using Whole-Genome SNP Genotypes

We propose a novel model (BayesN) for genomic prediction, where multiple markers in a small segment are simultaneously fitted to jointly capture the effect of major genes (QTL) in the segment. Compared with BayesB, in which the effects of neighboring markers are a prioriassumed to be independent, BayesN gave higher accuracies of prediction and required less computing effort. BayesN is an accurate and practical method for analyzing high-density markers, especially for traits influenced by rare QTL allele

Analysis of Ten Generations of Selection for Residual Feed Intake in Yorkshire Pigs

Ten generations (G) of divergent selection for residual feed intake (RFI) was practiced in Yorkshire pigs. This study shows that feed efficiency based on RFI was moderately heritable and responded to selection. Pigs selected for increased feed efficiency from the low RFI line ate less, grew slightly slower, and were leaner than pigs from the high RFI line. Thus, the results of this study show that selection for decreased RFI can improve feed efficiency and can be included in an economic selection index in addition to growth for reducing feed cost

Improved Accuracy of Genomic Prediction for Traits with Rare QTL by Fitting Haplotypes

Genomic prediction estimates breeding values by exploiting linkage disequilibrium (LD) between quantitative trait loci (QTL) and single nucleotide polymorphisms (SNPs). High LD cannot occur when QTL and SNPs have different minor allele frequencies (MAF). Marker panels tend to use SNPs with high MAF and will have limited ability to predict rare QTL alleles. In practice, increasing SNP density has not improved prediction accuracy. A possible reason is that many traits are characterized by rare QTL. In that case, linear models fitting haplotypes could have advantage because haplotypes can be in complete LD with QTL alleles. SNP genotypes were simulated to resemble 600K chip for the bovine genome. Genomic breeding values were predicted using either SNP genotypes or non-overlapping haplotypes. When QTL had low MAF, the haplotype model had significantly higher accuracy than the SNP model. Results show that fitting haplotypes can improve the accuracy of genomic prediction for traits controlled by rare QTL

On the Optical Activity of Steroidal 5,7-Dienes

Circular dichroism (CD) data are reported of a series of 9,10- stereoisomeric steroidal 5,7-dienes. In general the effects in the longest wavelength transition (270-280 nm) are large (Mm" 10---30) and consignate with respect to the diene helicity rule. The magnitude of the CD appears to vary markedly with the substituent at C-3 and at C-17, and with solvent. In the case of the 9a,10p-H dienes, variation of solvent and temperature can affect even the sign of the Cotton effect. This is explained from a change of geometry of the diene ring: solvation, substitution and temperature can affect the average geometry of the ring including the values of the angle of twist of the diene (ef> (6-7». The relevance of the observed chiroptical data for the theoretical description of the optical activity in the So-+ Sl transition of homoannular cisoid dienes is discussed

Recognising and defining a new crown clade within Stromboidea Rafinesque, 1815 (Mollusca, Gastropoda)

This paper defines a new crown clade Neostromboidea to separate the Strombidae, Rostellariidae, and Seraphsidae from their sister families Struthiolariidae and Aporrhaidae. There is significant value to understanding evolutionary processes within Stromboidea to recognise the universal similarity in the position of the eye on the end of peduncles and a diminished cephalic tentacle that arises from the middle to the end on that peduncle. This is in contrast to other members of the Stromboidea where the eye is located at the base of the cephalic tentacle. These physiological differences represent two set of organisms with divergent and independent evolutionary life histories and therefore these differences need to be identifiable within the nomenclature to bring meaning to the way we name things