Genome-wide association mapping for eyespot disease in US Pacific Northwest winter wheat.

Eyespot, caused by the soil-borne necrotrophic fungi Oculimacula yallundae and O. acuformis, is a disease of major economic significance for wheat, barley and rye. Pacific Northwest (PNW) winter wheat (Triticum aestivum L.) grown in areas of high rainfall and moderate winters is most vulnerable to infection. The objective of this research was to identify novel genomic regions associated with eyespot resistance in winter wheat adapted to the PNW. Two winter wheat panels of 469 and 399 lines were compiled for one of the first genome-wide association studies (GWAS) of eyespot resistance in US winter wheat germplasm. These panels were genotyped with the Infinium 9K and 90K iSelect SNP arrays. Both panels were phenotyped for disease resistance in a two-year field study and in replicated growth chamber trials. Growth chamber trials were used to evaluate the genetic resistance of O. acuformis and O. yallundae species separately. Best linear unbiased predictors (BLUPs) were calculated across all field and growth chamber environments. A total of 73 marker-trait associations (MTAs) were detected on nine different chromosomes (1A, 2A, 2B, 4A, 5A, 5B, 7A, 7B and 7D) that were significantly associated (p-value <0.001) with eyespot resistance in Panel A, and 19 MTAs on nine different chromosomes (1A, 1B, 2A, 2D, 3B, 5A, 5B, 7A, and 7B) in Panel B. The most significant SNPs were associated with Pch1 and Pch2 resistance genes on the long arms of chromosome 7D and 7A. Most of the novel MTAs appeared to have a minor effect on reducing eyespot disease. Nevertheless, eyespot disease scores decreased as the number of resistance alleles increased. Seven SNP markers, significantly associated with reducing eyespot disease across environments and in the absence and presence of Pch1 were identified. These markers were located on chromosomes 2A (IWB8331), 5A (IWB73709), 5B (IWB47298), 7AS (IWB47160), 7B (IWB45005) and two SNPs (Ex_c44379_2509 and IAAV4340) had unknown map positions. The additive effect of the MTAs explained most of the remaining phenotypic variation not accounted for by Pch1 or Pch2. This study provides breeders with adapted germplasm and novel sources of eyespot resistance to be used in the development of superior cultivars with increased eyespot resistance.

Characterizing and Validating Stripe Rust Resistance Loci in US Pacific Northwest Winter Wheat Accessions (Triticum aestivum L.) by Genome-wide Association and Linkage Mapping.

Stripe rust resistance is a critical need for wheat cultivars in the US Pacific Northwest (PNW). Our previous genome-wide association study (GWAS) for stripe rust resistance in a set of PNW winter wheat accessions (Panel-2) identified multiple marker-trait associations (MTAs) for both all-stage and field resistance. In this study, we conducted additional GWAS using a different set of PNW winter wheat accessions (Panel-1) that contained recently bred soft white winter wheat breeding lines and cultivars. A total of 12 all-stage resistance MTAs and eight field resistance MTAs were identified. Within these MTAs, nine MTAs for all-stage resistance and two MTAs for field resistance were located distinctly from previously characterized genes and likely represent novel loci. Markers IWB60567 (1B), IWB24342 (2A), and IWB46564 (2B) explained the largest phenotypic variances for disease responses. The analysis confirmed that MTAs on chromosome 1B were indeed the same as identified in Panel-2 and that MTAs on chromosome 2A were likely and closely linked to another field resistance QTL, (Panel-2). Haplotypes for MTAs on chromosome 1B, , and linked loci on chromosome 2A provide useful information for marker development and introgression of these QTL into wheat breeding programs.

Genetic Dissection of End-Use Quality Traits in Adapted Soft White Winter Wheat.

Soft white wheat is used in domestic and foreign markets for various end products requiring specific quality profiles. Phenotyping for end-use quality traits can be costly, time-consuming and destructive in nature, so it is advantageous to use molecular markers to select experimental lines with superior traits. An association mapping panel of 469 soft white winter wheat cultivars and advanced generation breeding lines was developed from regional breeding programs in the U.S. Pacific Northwest. This panel was genotyped on a wheat-specific 90 K iSelect single nucleotide polymorphism (SNP) chip. A total of 15,229 high quality SNPs were selected and combined with best linear unbiased predictions (BLUPs) from historical phenotypic data of the genotypes in the panel. Genome-wide association mapping was conducted using the Fixed and random model Circulating Probability Unification (FarmCPU). A total of 105 significant marker-trait associations were detected across 19 chromosomes. Potentially new loci for total flour yield, lactic acid solvent retention capacity, flour sodium dodecyl sulfate sedimentation and flour swelling volume were also detected. Better understanding of the genetic factors impacting end-use quality enable breeders to more effectively discard poor quality germplasm and increase frequencies of favorable end-use quality alleles in their breeding populations.

Genome-Wide Association Mapping for Tolerance to Preharvest Sprouting and Low Falling Numbers in Wheat.

Preharvest sprouting (PHS), the germination of grain on the mother plant under cool and wet conditions, is a recurring problem for wheat farmers worldwide. α-amylase enzyme produced during PHS degrades starch resulting in baked good with poor end-use quality. The Hagberg-Perten Falling Number (FN) test is used to measure this problem in the wheat industry, and determines how much a farmer's wheat is discounted for PHS damage. PHS tolerance is associated with higher grain dormancy. Thus, breeding programs use germination-based assays such as the spike-wetting test to measure PHS susceptibility. Association mapping identified loci associated with PHS tolerance in U.S. Pacific Northwest germplasm based both on FN and on spike-wetting test data. The study was performed using a panel of 469 white winter wheat cultivars and elite breeding lines grown in six Washington state environments, and genotyped for 15,229 polymorphic markers using the 90k SNP Illumina iSelect array. Marker-trait associations were identified using the FarmCPU R package. Principal component analysis was directly and a kinship matrix was indirectly used to account for population structure. Nine loci were associated with FN and 34 loci associated with PHS based on sprouting scores. None of the QFN.wsu loci were detected in multiple environments, whereas six of the 34 QPHS.wsu loci were detected in two of the five environments. There was no overlap between the QTN detected based on FN and PHS, and there was little correlation between the two traits. However, both traits appear to be PHS-related since 19 of the 34 QPHS.wsu loci and four of the nine QFN.wsu loci co-localized with previously published dormancy and PHS QTL. Identification of these loci will lead to a better understanding of the genetic architecture of PHS and will help with the future development of genomic selection models.

Genomic Regions Associated with Tolerance to Freezing Stress and Snow Mold in Winter Wheat.

Plants grown through the winter are subject to selective pressures that vary with each year's unique conditions, necessitating tolerance of numerous abiotic and biotic stress factors. The objective of this study was to identify molecular markers in winter wheat (Triticum aestivum L.) associated with tolerance of two of these stresses, freezing temperatures and snow mold-a fungal disease complex active under snow cover. A population of 155 F2:5 recombinant inbred lines from a cross between soft white wheat cultivars "Finch" and "Eltan" was evaluated for snow mold tolerance in the field, and for freezing tolerance under controlled conditions. A total of 663 molecular markers was used to construct a genetic linkage map and identify marker-trait associations. One quantitative trait locus (QTL) associated with both freezing and snow mold tolerance was identified on chromosome 5A. A second, distinct, QTL associated with freezing tolerance also was found on 5A, and a third on 4B. A second QTL associated with snow mold tolerance was identified on chromosome 6B. The QTL on 5A associated with both traits was closely linked with the Fr-A2 (Frost-Resistance A2) locus; its significant association with both traits may have resulted from pleiotropic effects, or from greater low temperature tolerance enabling the plants to better defend against snow mold pathogens. The QTL on 4B associated with freezing tolerance, and the QTL on 6B associated with snow mold tolerance have not been reported previously, and may be useful in the identification of sources of tolerance for these traits.

Corticosteroid Treatments in Males With Duchenne Muscular Dystrophy: Treatment Duration and Time to Loss of Ambulation.

This population-based study examines the association between corticosteroid treatment and time to loss of ambulation, stratifying by treatment duration (short: 0.25-3 years, long: >3 years), among 477 Duchenne muscular dystrophy cases identified by the Muscular Dystrophy Surveillance Tracking and Research Network (MDSTARnet). Those cases who received short-term corticosteroid treatment had a time to loss of ambulation that was 0.8 years shorter (t test) and an annual risk of losing ambulation 77% higher than the untreated (Cox regression). Conversely, cases who received long-term corticosteroid treatment had a time to loss of ambulation that was 2 years longer and an annual risk of losing ambulation 82% lower than the untreated, up to age 11 years; after which the risks were not statistically different. The relationship of corticosteroids and time to loss of ambulation is more complex than depicted by previous studies limited to treatment responders or subjects who lost ambulation during study follow-up.

Mapping stripe rust resistance in a BrundageXCoda winter wheat recombinant inbred line population.

A recombinant inbred line (RIL) mapping population developed from a cross between winter wheat (Triticum aestivum L.) cultivars Coda and Brundage was evaluated for reaction to stripe rust (caused by Puccinia striiformis f. sp. tritici). Two hundred and sixty eight RIL from the population were evaluated in replicated field trials in a total of nine site-year locations in the U.S. Pacific Northwest. Seedling reaction to stripe rust races PST-100, PST-114 and PST-127 was also examined. A linkage map consisting of 2,391 polymorphic DNA markers was developed covering all chromosomes of wheat with the exception of 1D. Two QTL on chromosome 1B were associated with adult plant and seedling reaction and were the most significant QTL detected. Together these QTL reduced adult plant infection type from a score of seven to a score of two reduced disease severity by an average of 25% and provided protection against race PST-100, PST-114 and PST-127 in the seedling stage. The location of these QTL and the race specificity provided by them suggest that observed effects at this locus are due to a complementation of the previously known but defeated resistances of the cultivar Tres combining with that of Madsen (the two parent cultivars of Coda). Two additional QTL on chromosome 3B and one on 5B were associated with adult plant reaction only, and a single QTL on chromosome 5D was associated with seedling reaction to PST-114. Coda has been resistant to stripe rust since its release in 2000, indicating that combining multiple resistance genes for stripe rust provides durable resistance, especially when all-stage resistance genes are combined in a fashion to maximize the number of races they protect against. Identified molecular markers will allow for an efficient transfer of these genes into other cultivars, thereby continuing to provide excellent resistance to stripe rust.

Use of complementary and alternative medicine by males with Duchenne or Becker muscular dystrophy.

Use of complementary and alternative medicine by males with Duchenne or Becker muscular dystrophy was examined using interview reports from caregivers enrolled in the population-based Muscular Dystrophy Surveillance, Tracking, and Research Network. Of the 200 caregivers interviewed, 160 (80%) reported "ever" using complementary and alternative medicine for their affected children. Mind-body medicine (61.5%) was most frequently used, followed by biologically based practices (48.0%), manipulative and body-based practices (29.0%), and whole medical systems (8.5%). Caregivers reporting use of whole medical systems had higher education and income levels compared with nonusers; affected males had shorter disease duration. Caregivers reporting use of mind-body medicine, excluding aquatherapy, had higher education level compared with nonusers. Overall, complementary and alternative medicine use was high; disease duration, education, and income levels influenced use. These findings have implications for developing clinical care protocols and monitoring possible interactions between complementary and alternative medicine and conventional medical therapies.

Maternal bronchodilator use and the risk of orofacial clefts.

BACKGROUND: Few epidemiological studies have explored the relationship between orofacial clefts and bronchodilators. We assessed whether mothers who used bronchodilators during early pregnancy were at an increased risk of delivering infants with orofacial clefts. METHODS: We used National Birth Defects Prevention Study case-control data from mothers of 2711 infants with orofacial clefts and 6482 mothers of live born infants without birth defects, delivered during 1997 through 2005. Information on medication use from 3 months before pregnancy through delivery was collected using a standardized interview. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) for maternal bronchodilator use during the periconceptional period (1 month before pregnancy through the third month of pregnancy) while controlling for other covariates. RESULTS: We observed an association between maternal bronchodilator use during the periconceptional period and cleft lip only (CLO) (aOR = 1.77, 95% CI: 1.08-2.88). The risk of cleft palate only (CPO) (aOR = 1.53, 95% CI: 0.99-2.37) was elevated but was not statistically significant. No association was observed for maternal bronchodilator use and the risk of cleft lip with cleft palate (aOR = 0.78, 95% CI: 0.46-1.31). The most commonly used bronchodilator was albuterol (88.7%). Maternal albuterol use was associated with CLO (aOR = 1.79, 95% CI: 1.07-2.99) and CPO (aOR = 1.65, 95% CI: 1.06-2.58). CONCLUSIONS: We observed a statistically significant association between maternal bronchodilator use during the periconceptional period and the risk of CLO after controlling for other risk factors. It is unclear whether the increased odds ratios observed in this study are due to the bronchodilators, the severity of asthma, or both, or to chance alone. Further studies to disentangle the role of asthma or asthma medications would help clarify these findings.

Use of corticosteroids in a population-based cohort of boys with duchenne and becker muscular dystrophy.

The use of corticosteroids for treatment of Duchenne and Becker muscular dystrophy in clinical practice from 1991 through 2005 was reviewed in a large population-based cohort (MD STARnet) of boys in 4 regional sites and 6 clinics of the United States. Corticosteroid use increased from 20% (11 of 56 individuals) in 1991 to 44% (93 of 218 individuals) in 2005. Average use varied by site and ranged from 15% to 49%. The median age of corticosteroid initiation was 6.9 years (range, 3.7-17.4 years). Dosage and growth information was available for 102 participants and showed a median dose as 0.729 mg/kg for prednisone and 0.831 mg/kg for deflazacort. T. The most common reasons that corticosteroids were discontinued included weight gain, behavioral side effects, and loss of ambulation, resulting in full-time wheelchair use. Substantial variations in clinical practice were identified among study sites.

Ab initio and microcalorimetric investigations of alkene adsorption on phosphotungstic acid.

The adsorption of ethene, propene, 1-butene, trans-2-butene, and isobutene on phosphotungstic acid has been characterized by density functional theory (DFT) calculations and microcalorimetric experiments. The DFT-calculated chemisorption energies to form the corresponding alkoxides for ethene, propene, 1-butene, trans-2-butene, and isobutene were -86.8, -90.3, -102.6, -79.9, and -91.4 kJ mol(-1), respectively (for their most-favorable binding modes). The relative chemisorption energies to form the alkoxides are dictated by the strength of interaction of the acidic proton with the carbon atom of the double bond that becomes protonated. The activation barrier for chemisorption was greatest for alkenes with primary (1 degrees) carbenium-like transition states followed by secondary (2 degrees) and tertiary (3 degrees) transition states. The adsorption enthalpy established from microcalorimetric experiments with propene and isobutene was approximately -100 kJ mol(-1), which is close to the DFT-calculated values. Chemisorption of ethene on phosphotungstic acid during microcalorimetric experiments was minimal, presumably because of the large activation barrier associated with a 1 degrees carbenium-like transition state. The results from this study are compared with those in the literature for the adsorption of alkenes on zeolites, which have a similar adsorption mechanism. Our results suggest that alkene adsorption is stronger on phosphotungstic acid than on zeolites, as supported by the more exothermic chemisorption energies. Additionally, activation barriers for alkene adsorption are lower over phosphotungstic acid than over zeolites.