Effect of population structure corrections on the results of association mapping tests in complex maize diversity panels

Association mapping of sequence polymorphisms underlying the phenotypic variability of quantitative agronomical traits is now a widely used method in plant genetics. However, due to the common presence of a complex genetic structure within the plant diversity panels, spurious associations are expected to be highly frequent. Several methods have thus been suggested to control for panel structure. They mainly rely on ad hoc criteria for selecting the number of ancestral groups; which is often not evident for the complex panels that are commonly used in maize. It was thus necessary to evaluate the effect of the selected structure models on the association mapping results. A real maize data set (342 maize inbred lines and 12,000 SNPs) was used for this study. The panel structure was estimated using both Bayesian and dimensional reduction methods, considering an increasing number of ancestral groups. Effect on association tests depends in particular on the number of ancestral groups and on the trait analyzed. The results also show that using a high number of ancestral groups leads to an over-corrected model in which all causal loci vanish. Finally the results of all models tested were combined in a meta-analysis approach. In this way, robust associations were highlighted for each analyzed trait

Comparative SNP and Haplotype Analysis Reveals a Higher Genetic Diversity and Rapider LD Decay in Tropical than Temperate Germplasm in Maize

Understanding of genetic diversity and linkage disequilibrium (LD) decay in diverse maize germplasm is fundamentally important for maize improvement. A total of 287 tropical and 160 temperate inbred lines were genotyped with 1943 single nucleotide polymorphism (SNP) markers of high quality and compared for genetic diversity and LD decay using the SNPs and their haplotypes developed from genic and intergenic regions. Intronic SNPs revealed a substantial higher variation than exonic SNPs. The big window size haplotypes (3-SNP slide-window covering 2160 kb on average) revealed much higher genetic diversity than the 10 kb-window and gene-window haplotypes. The polymorphic information content values revealed by the haplotypes (0.436–0.566) were generally much higher than individual SNPs (0.247–0.259). Cluster analysis classified the 447 maize lines into two major groups, corresponding to temperate and tropical types. The level of genetic diversity and subpopulation structure were associated with the germplasm origin and post-domestication selection. Compared to temperate lines, the tropical lines had a much higher level of genetic diversity with no significant subpopulation structure identified. Significant variation in LD decay distance (2–100 kb) was found across the genome, chromosomal regions and germplasm groups. The average of LD decay distance (10–100 kb) in the temperate germplasm was two to ten times larger than that in the tropical germplasm (5–10 kb). In conclusion, tropical maize not only host high genetic diversity that can be exploited for future plant breeding, but also show rapid LD decay that provides more opportunity for selection

Determination of genetic structure of germplasm collections: are traditional hierarchical clustering methods appropriate for molecular marker data?

Despite the availability of newer approaches, traditional hierarchical clustering remains very popular in genetic diversity studies in plants. However, little is known about its suitability for molecular marker data. We studied the performance of traditional hierarchical clustering techniques using real and simulated molecular marker data. Our study also compared the performance of traditional hierarchical clustering with model-based clustering (STRUCTURE). We showed that the cophenetic correlation coefficient is directly related to subgroup differentiation and can thus be used as an indicator of the presence of genetically distinct subgroups in germplasm collections. Whereas UPGMA performed well in preserving distances between accessions, Ward excelled in recovering groups. Our results also showed a close similarity between clusters obtained by Ward and by STRUCTURE. Traditional cluster analysis can provide an easy and effective way of determining structure in germplasm collections using molecular marker data, and, the output can be used for sampling core collections or for association studies

Application of Surface wave methods for seismic site characterization

Surface-wave dispersion analysis is widely used in geophysics to infer a shear wave velocity model of the subsoil for a wide variety of applications. A shear-wave velocity model is obtained from the solution of an inverse problem based on the surface wave dispersive propagation in vertically heterogeneous media. The analysis can be based either on active source measurements or on seismic noise recordings. This paper discusses the most typical choices for collection and interpretation of experimental data, providing a state of the art on the different steps involved in surface wave surveys. In particular, the different strategies for processing experimental data and to solve the inverse problem are presented, along with their advantages and disadvantages. Also, some issues related to the characteristics of passive surface wave data and their use in H/V spectral ratio technique are discussed as additional information to be used independently or in conjunction with dispersion analysis. Finally, some recommendations for the use of surface wave methods are presented, while also outlining future trends in the research of this topic

Seropositivity rates for agents of canine vector-borne diseases in Spain : a multicentre study

Background: Controlling canine vector-borne diseases (CVBD) is a major concern, since some of these diseases are serious zoonoses. This study was designed to determine seropositivity rates in Spain for agents causing the following five CVBD: leishmaniosis (Leishmania infantum: Li), heartworm (Dirofilaria immitis: Di), ehrlichiosis (Ehrlichia canis: Ec), anaplasmosis (Anaplasma phagocytophilum/Anaplasma platys: An) and Lyme disease (Borrelia burgdorferi: Bb). Methods: Anti-An, -Bb, and -Ec antibodies and the Di antigen were determined using the 4DX SNAP® Test (IDEXX Laboratories) and anti-L. infantum (Li) antibodies using the Leishmania SNAP® Test (IDEXX Laboratories) in blood and/or serum samples. Results: Among 1100 dogs examined, overall seropositivity rates were: Li (15.7%), Ec (5%), An (3.1%), Di (1.25%) and Bb (0.4%). While seropositivity towards Bb and Di was similar in all geographic regions, rates were significantly higher in the east of Spain (8.3%) for An, significantly higher in the north (20%) for Ec, and significantly higher in the Southeast (46.6%) and South (27.4%), and significantly lower in the north (0%) for Li. No statistical associations were observed between sex and the CVBD analyzed (p ≥ 0.05) while the following associations with other variables were detected: a higher seropositivity to Ec (40%) and Bb (6.7%) in dogs under one year of age compared with adults (p < 0.05); and a higher seropositivity to An and Li in dogs that lived outdoors versus indoors (p = 0.01; p < 0.001, respectively). Seropositivity rates of 2.1%, 0%, 1.7%, 0.5% and 4.2% were recorded respectively for An, Bb, Ec, Di and Li in dogs with no clinical signs (n = 556) versus 3.8%, 0.6%, 7.5%, 1.8% and 25.9% for those with signs (n = 507) suggestive of a CVBD. Conclusion: The data obtained indicate a risk for dogs in Spain of acquiring any of the five CVBD examined. Veterinarians in the different regions should include these diseases in their differential diagnoses and recommend the use of repellents and other prophylactic measures to prevent disease transmission by arthropod vectors. Public health authorities also need to become more involved in the problem, since some of the CVBD examined here also affect humans

Exercise therapy in Type 2 diabetes

Structured exercise is considered an important cornerstone to achieve good glycemic control and improve cardiovascular risk profile in Type 2 diabetes. Current clinical guidelines acknowledge the therapeutic strength of exercise intervention. This paper reviews the wide pathophysiological problems associated with Type 2 diabetes and discusses the benefits of exercise therapy on phenotype characteristics, glycemic control and cardiovascular risk profile in Type 2 diabetes patients. Based on the currently available literature, it is concluded that Type 2 diabetes patients should be stimulated to participate in specifically designed exercise intervention programs. More attention should be paid to cardiovascular and musculoskeletal deconditioning as well as motivational factors to improve long-term treatment adherence and clinical efficacy. More clinical research is warranted to establish the efficacy of exercise intervention in a more differentiated approach for Type 2 diabetes subpopulations within different stages of the disease and various levels of co-morbidity

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events