A novel CCCH‐type zinc finger protein SAW1 activates OsGA20ox3 to regulate gibberellin homeostasis and anther development in rice

Male sterility is a prerequisite for hybrid seed production. The phytohormone gibberellin (GA) is involved in regulating male reproductive development, but the mechanism underlying GA homeostasis in anther development remains less understood. Here, we report the isolation and characterization of a new positive regulator of GA homeostasis, swollen anther wall 1 (SAW1), for anther development in rice (Oryza sativa L.). Rice plants carrying the recessive mutant allele saw1 produces abnormal anthers with swollen anther wall and aborted pollen. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRIPSR‐associated protein 9‐mediated knockout of SAW1 in rice generated similar male sterile plants. SAW1 encodes a novel nucleus‐localizing CCCH‐tandem zinc finger protein, and this protein could directly bind to the promoter region of the GA synthesis gene OsGA20ox3 to induce its anther‐specific expression. In the saw1 anther, the significantly decreased OsGA20ox3 expression resulted in lower bioactive GA content, which in turn caused the lower expression of the GA‐inducible anther‐regulator gene OsGAMYB. Thus, our results disclose the mechanism of the SAW1‐GA20ox3‐GAMYB pathway in controlling rice anther development, and provide a new target gene for the rapid generation of male sterile lines by genome editing for hybrid breeding.     

Efficient p-value evaluation for resampling-based tests

The resampling-based test, which often relies on permutation or bootstrap procedures, has been widely used for statistical hypothesis testing when the asymptotic distribution of the test statistic is unavailable or unreliable. It requires repeated calculations of the test statistic on a large number of simulated data sets for its significance level assessment, and thus it could become very computationally intensive. Here, we propose an efficient p-value evaluation procedure by adapting the stochastic approximation Markov chain Monte Carlo algorithm. The new procedure can be used easily for estimating the p-value for any resampling-based test. We show through numeric simulations that the proposed procedure can be 100-500 000 times as efficient (in term of computing time) as the standard resampling-based procedure when evaluating a test statistic with a small p-value (e.g. less than 10( - 6)). With its computational burden reduced by this proposed procedure, the versatile resampling-based test would become computationally feasible for a much wider range of applications. We demonstrate the application of the new method by applying it to a large-scale genetic association study of prostate cancer.     

Analysis on the interaction between IL-1F7 gene and environmental factors on patients with ankylosing spondylitis: a case-only study

To examine the interaction between IL-1F7 gene and environmental factors in patients with ankylosing spondylities (AS). 150 AS Han Chinese patients (all human leukocyte antigen-B27 positive) were genotyped using a panel of single-nucleotide polymorphism markers within IL-1F7 gene (rs3811047) by ligase detection reactions. Polymerase chain reaction with sequence-specific primer was used to determine HLA-B27 subtypes. We analyzed the interaction between IF-1F7 gene and eight environmental factors in AS patients by using a case-only study. The genetic polymorphism and environmental factors were considered as dependent variables in logistic models, and P-values, ORi and 95% confidence intervals were used for estimating the effects of interaction. The different frequency of A/G between drinking group and non-drinking group was significant (ORi 3.163, 95% CI 1.368-7.317, P=0.006). Within the cooking oil group, odds ratio for interaction of G×E between main plants fats and half plants -half animal fats subunits was 4.273 (95% CI 1.590-11.479, P=0.004). Our data show that there was no interaction between IL-1F7 alleles and the other six environmental factors in AS patients (all P>0.05). We observed that there was an interaction between IF-1F7 gene and drinking in AS patients. Thus, drinking may be a risk exposure factor to take combined action with predisposing genes in AS patients. This action may increase the incident risk of AS. Also, main plants fats may be protective factors to AS.     

Exploiting comparative mapping among Brassica species to accelerate the physical delimitation of a genic male-sterile locus (BnRf) in Brassica napus

The recessive genic male sterility (RGMS) line 9012AB has been used as an important pollination control system for rapeseed hybrid production in China. Here, we report our study on physical mapping of one male-sterile locus (BnRf) in 9012AB by exploiting the comparative genomics among Brassica species. The genetic maps around BnRf from previous reports were integrated and enriched with markers from the Brassica A7 chromosome. Subsequent collinearity analysis of these markers contributed to the identification of a novel ancestral karyotype block F that possibly encompasses BnRf. Fourteen insertion/deletion markers were further developed from this conserved block and genotyped in three large backcross populations, leading to the construction of high-resolution local genetic maps where the BnRf locus was restricted to a less than 0.1-cM region. Moreover, it was observed that the target region in Brassica napus shares a high collinearity relationship with a region from the Brassica rapa A7 chromosome. A BnRf-cosegregated marker (AT3G23870) was then used to screen a B. napus bacterial artificial chromosome (BAC) library. From the resulting 16 positive BAC clones, one (JBnB089D05) was identified to most possibly contain the BnRf (c) allele. With the assistance of the genome sequence from the Brassica rapa homolog, the 13.8-kb DNA fragment covering both closest flanking markers from the BAC clone was isolated. Gene annotation based on the comparison of microcollinear regions among Brassica napus, B. rapa and Arabidopsis showed that five potential open reading frames reside in this fragment. These results provide a foundation for the characterization of the BnRf locus and allow a better understanding of the chromosome evolution around BnRf.     

Association of microRNA-499 rs3746444 Polymorphism with Cancer Risk: Evidence from 7188 Cases and 8548 Controls

Background

Owing to inconsistent and inconclusive results, we performed a meta-analysis to derive a more precise estimation of the association between miR-499 rs3746444 polymorphism and cancer risk.

Methodology/Principal Findings

A systematic search of the Pubmed, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) databases was performed with the last search updated on May 6, 2012. The odds ratio (OR) and its 95% confidence interval (95%CI) were used to assess the strength of the association. A total of 15 independent studies including 7,188 cases and 8,548 controls were used in the meta-analysis. In the present meta-analysis, we found a significant association between miR-499 rs3746444 polymorphism and cancer risk in the overall analysis (G versus A: OR = 1.10, 95%CI 1.01–1.19, P = 0.03; GG+AG versus AA: OR = 1.15, 95%CI 1.02–1.30, P = 0.02; GG versus AG+AA: OR = 1.07, 95%CI 0.89–1.28, P = 0.50; GG versus AA: OR = 1.13, 95%CI 0.98–1.31, P = 0.09; AG versus AA: OR = 1.16, 95%CI 1.02–1.33, P = 0.03). In the subgroup analysis by ethnicity, miR-499 rs3746444 polymorphism was significantly associated with cancer risk in Asian population. In the subgroup analysis by cancer types, miR-499 rs3746444 polymorphism was significantly associated with breast cancer.

Conclusions/Significance

This meta-analysis suggests a significant association between miR-499 rs3746444 polymorphism and cancer risk. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.     

Molecular validation of a multiple-allele recessive genic male sterility locus (BnRf) in Brassica napus L.

The recessive genic male sterility (RGMS) line 9012AB has been used successfully for rapeseed hybrid production in China. This male sterility was previously thought to be controlled by three independent genes (Bnms3, Bnms4, and BnRf). Here, we initially attempted to locate the BnMs4 locus and develop feasible molecular markers for application in practical rapeseed breeding. However, we found that three sequence characterized amplified region markers and five simple sequence repeat markers identified as linked to BnMs4 were also genetically associated with BnRf, suggesting the possible co-localization of these two loci. Moreover, we proved that four intron-based polymorphism markers tightly linked or co-segregated with BnRf could also be mapped to BnMs4 with a genetic distance ranging from 0.054 to 0.594?cM. Finally, integration of genetic maps around BnRf and BnMs4 allows for the physical restriction of both loci to a DNA fragment of about 50?kb. Systematic genetic tests also provided evidence that the candidate BnMs4 locus was allelic to the BnRf locus. These results confirmed a major modification of the sterility inheritance model in 9012A: specifically, that this male sterility was essentially controlled by two loci (BnMs3 and BnRf), whereas the previously designated BnMs4 locus (hereafter designated as BnRf ^a ) was just one allele of BnRf in addition to BnRf ^b (the allele from 9012A) and BnRf ^c (the allele from temporary maintainer), with a dominance relationship of BnRf ^a ?>?BnRf ^b ?>?BnRf ^c . This inheritance model will simplify the breeding process involved with this RGMS line, especially with the BnRf allele-specific molecular markers identified here.     

A flexible Bayesian model for studying gene-environment interaction

An important follow-up step after genetic markers are found to be associated with a disease outcome is a more detailed analysis investigating how the implicated gene or chromosomal region and an established environment risk factor interact to influence the disease risk. The standard approach to this study of gene–environment interaction considers one genetic marker at a time and therefore could misrepresent and underestimate the genetic contribution to the joint effect when one or more functional loci, some of which might not be genotyped, exist in the region and interact with the environment risk factor in a complex way. We develop a more global approach based on a Bayesian model that uses a latent genetic profile variable to capture all of the genetic variation in the entire targeted region and allows the environment effect to vary across different genetic profile categories. We also propose a resampling-based test derived from the developed Bayesian model for the detection of gene–environment interaction. Using data collected in the Environment and Genetics in Lung Cancer Etiology (EAGLE) study, we apply the Bayesian model to evaluate the joint effect of smoking intensity and genetic variants in the 15q25.1 region, which contains a cluster of nicotinic acetylcholine receptor genes and has been shown to be associated with both lung cancer and smoking behavior. We find evidence for gene–environment interaction (P-value = 0.016), with the smoking effect appearing to be stronger in subjects with a genetic profile associated with a higher lung cancer risk; the conventional test of gene–environment interaction based on the single-marker approach is far from significant.     

不同浓度硒酸钠对茶树的生长和生理指标的影响

该文以一年生扦插苗为材料,采用水培试验,研究不同浓度的硒酸钠(0、0.15、0.3、1.5、3、5、8 mg·L^-1)对茶苗的硒积累、植株生长、生理指标和根尖显微结构等参数的影响。结果表明:茶苗的根和新梢中的硒含量与营养液中的硒浓度正相关;随着硒浓度升高,茶苗的鲜重、侧根数量、根系生物量、光合色素含量、根系活力等生长指标,茶多酚、可溶性蛋白、可溶性糖等茶叶质量指标均呈现先升后降趋势;而丙二醛、过氧化氢、脯氨酸含量等抗逆生理指标则呈现先降后升趋势。显微结构分析显示在不同硒浓度处理条件下根尖的显微构造存在差异。低硒浓度(0.15、0.3、1.5 mg·L^-1)处理的茶苗根尖的皮层薄壁细胞饱满、完好,表皮细胞较小;高硒浓度(Se≥3 mg·L^-1)处理的茶苗根尖的皮层薄壁细胞变形或受损,表皮细胞增厚,表现出胁迫反应。上述结果说明硒对茶树具有双重效应,合适浓度(0.3 mg·L^-1)硒对茶树生长和茶叶品质有益,表现为光合作用和根系活力增强,过氧化物和脯氨酸含量降低,生物量增加,茶叶茶多酚含量增加;硒浓度过高(≥3 mg·L^-1)对茶苗的生长和茶叶品质有害,表现为茶苗出现胁迫反应,茶多酚降低。该研究结果为进一步研究硒对茶树的双重作用机制和富硒茶的栽培提供参考。     

Copy number variations and polymorphisms in HSP90AB1 and risk of systemic lupus erythematosus and efficacy of glucocorticoids

The aim of our study was to assess the associations of HSP90AB1 copy number variations (CNVs) with systemic lupus erythematosus (SLE) risk and glucocorticoids (GCs) efficacy, as well as the relationship between HSP90AB1 single‐nucleotide polymorphisms (SNPs) and GCs efficacy. HSP90AB1 CNVs and SLE risk were analysed in 519 patients and 538 controls. Patients treated with GCs were followed up for 12 weeks and were divided into sensitive and insensitive groups to investigate the effects of CNVs (419 patients) and SNPs (457 patients) on the efficacy of GCs. Health‐related quality of life (HRQoL) was also measured by SF‐36 at baseline and week 12 to explore the relationship between CNVs/SNPs and HRQoL improvements in Chinese SLE patients. Our results indicated a statistically significant association between HSP90AB1 CNVs and SLE (P_BH = 0.039), and this association was more pronounced in the female subgroup (P_BH = 0.039). However, we did not detect association of HSP90AB1 CNVs/SNPs with efficacy of GCs. But we found a marginal association between SNP rs13296 and improvement in Role‐emotional, while this association was not strong enough to survive in the multiple testing corrections. Collectively, our findings suggest that the copy number of HSP90AB1 is associated with SLE susceptibility. But copy number and polymorphisms of HSP90AB1 may not be associated with efficacy of GCs.