The genetic architecture of a complex trait: Resistance to multiple toxins produced by Bacillus thuringiensis israelensis in the dengue and yellow fever vector,the mosquito Aedes aegypti

The bacterial insecticide Bacillus thuringiensis subsp. israelensis (Bti) is an increasingly popular alternative to chemical insecticides for controlling mosquito populations. Because Bti toxicity relies on the action of four main toxins, resistance to Bti is very likely a complex phenotype involving several genes simultaneously. Dissecting the underlying genetic basis thus requires associating a quantitative measure of resistance to genetic variation at many loci in a segregating population. Here, we undertake this task using the dengue and yellow fever vector, the mosquito Aedes aegypti, as a study model. We conducted QTL (Quantitative Trait Locus) and admixture mapping analyses on two controlled crosses and on an artificial admixed population, respectively, all obtained from resistant and susceptible lab strains. We detected 16 QTL regions, among which four QTLs were revealed by different analysis methods. These four robust QTLs explained altogether 29.2% and 62.2% of the total phenotypic variance in the two QTL crosses, respectively. They also all showed a dominant mode of action. In addition, we found six loci showing statistical association with Bti resistance in the admixed population. Five of the supercontigs highlighted in this study contained candidate genes as suggested by their function, or by prior evidence from expression and/or outlier analyses. These genomic regions are thus good starting points for fine mapping of resistance to Bti or functional analyses aiming at identifying the underlying genes and mutations. Moreover, for the purpose of this work, we built the first Ae. aegypti genetic map based on markers associated with genes expressed in larvae. This genetic map harbors 229 SNP markers mapped across the three chromosomes for a total length of 311.9 cM. It brought to light several assembly discrepancies with the reference genome, suggesting a high level of genome plasticity in Ae. aegypti.     

Discovery of a new gene pool and a high genetic diversity of the chestnut blight fungus Cryphonectria parasitica in Caucasian Georgia

In this study, we investigated the population genetic structure and possible origins of the plant pathogen Cryphonectria parasitica in Caucasian Georgia, a region within the centre of origin of the host species Castanea sativa. A total of 427 C. parasitica isolates from nine populations were genotyped at 10 microsatellite loci. A high genetic diversity was detected, but the overall Georgian population was dominated by three haplotypes which were present in most individual populations. Two of them have not been previously found in Europe. Bayesian clustering analysis and principal component analysis could not identify their source population, neither in Asia nor in North America. On the other hand, one haplotype is frequent in Central Europe and probably naturally invaded Caucasian Georgia from neighbouring Turkey. Seventy-three haplotypes were unique to specific populations, and 66 of them were represented by a single isolate. Allele patterns suggest that most of these haplotypes emerged locally through sexual recombination between haplotypes of the Georgian and the central European gene pool. Due to the high incidence of haplotypes not otherwise present in Europe, Caucasian Georgia represents an additional source of diversity for the European C. parasitica population.     

Genetic diversity of HLA system in four populations from Baja California,Mexico: Mexicali,La Paz,Tijuana and rural Baja California

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 250 Mexicans from the states of Baja California Norte and Baja California Sur living in Mexicali (N = 100), La Paz (N = 75), Tijuana (N = 25) and rural communities (N = 50) to obtain information regarding allelic and haplotypic frequencies. The most frequent haplotypes for the Baja California region include nine Native American and five European haplotypes. Admixture estimates revealed that the main genetic components are European (50.45 ± 1.84% by ML; 42.03% of European haplotypes) and Native American (43.72 ± 2.36% by ML; 40.24% of Native American haplotypes), while the African genetic component was less apparent (5.83 ± 0.98% by ML; 9.36% of African haplotypes).     

我院静脉药物配置中心不合理用药医嘱分析

目的:分析某院静脉药物配置中心的不合理用药医嘱情况。方法:统计某院2011年8月至2013年6月审核发现的不合理用药医嘱,对其进行分类并分析。结果:21个月来执行医嘱共705 883条,不合理用药医嘱554条(0.08%),类型包括剂量不当、配伍禁忌、溶媒选择不合理等。结论:该院PIVAS的开展对于促进临床合理用药具有重要的作用和现实意义。     

Genetic diversity of HLA system in three populations from Sonora,Mexico: Ciudad Obregón,Hermosillo and rural Sonora

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 439 Mexicans from the state of Sonora living in Ciudad Obregón (N = 143), Hermosillo (N = 99), and rural communities (N = 197) to obtain information regarding allelic and haplotypic frequencies. We find that the 13 most frequent haplotypes for the state of Sonora include nine Native American, three European and one Asian haplotypes. Admixture estimates revealed that the main genetic components in the state of Sonora are European (51.25 ± 2.90% by ML; 37.70% of European haplotypes) and Native American (43.35 ± 2.57% by ML; 39.64% of Native American haplotypes), while the African genetic component was less apparent (5.39 ± 2.54% by ML; 11.04% of African haplotypes).     

Genetic diversity of HLA system in six populations from Jalisco,Mexico: Guadalajara city,Tlajomulco, Tlaquepaque,Tonalá, Zapopan and rural Jalisco

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 2046 Mexicans from the state of Jalisco living in the city of Guadalajara (N = 1189), Tlajomulco (N = 30), Tlaquepaque (N = 39), Tonalá (N = 35), Zapopan (N = 168) and rural communities (N = 585), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes found in the state of Jalisco include nine Native American most probable ancestry and three European haplotypes. Admixture estimates revealed that the main genetic components in the state of Jalisco are European (48.45 ± 1.18% by ML; 41.66% of European haplotypes) and Native American (44.02 ± 1.24% by ML; 39.86% of Native American haplotypes), while African genetic component is less apparent (7.53 ± 0.30% by ML; 9.62% of African haplotypes).     

细胞毒药物集中配置中必须注意的一些问题

目的:防止细胞毒药物对医务人员的危害,保证配置药品质量。方法:介绍细胞毒药物的潜在危害性,阐述我院静脉药物配置中心在防护和管理上的特点,强调须注意的一些问题。结果:目前我院尚未发现有医务人员发生与细胞毒药物相关的职业危害。结论:只要严格遵循有关安全操作规程,采取防护措施,可以避免接触细胞毒药物时产生的危害。     

Unexpected inverse correlation between Native American ancestry and Asian American variants of HPV16 in admixed Colombian cervical cancer cases

BackgroundEuropean (E) variants of HPV 16 are evenly distributed among world regions, meanwhile Non-European variants such as European-Asian (EAs), Asian American (AA) and African (Af) are mostly confined to Eastern Asia, The Americas and African regions respectively. Several studies have shown that genetic variation of HPV 16 is associated with the risk of cervical cancer, which also seems to be dependent on the population. This relationship between ethnicity and variants have led to the suggestion that there is co-evolution of variants with humankind. Our aim was to evaluate the relationship between the individual ancestry proportion and infection with HPV 16 variants in cervical cancer.MethodsWe examined the association between ancestry and HPV 16 variants in samples of 82 cervical cancer cases from different regions of Colombia. Individual ancestry proportions (European, African and Native American) were estimated by genotyping 106 ancestry informative markers. Variants were identified by PCR amplification of the E6 gene, followed by reverse line blot hybridization (RLB) with variants specific probes.ResultsOverall European (E) and Asian American (AA) variants frequency was 66.5% and 33.5% respectively. Similar distribution was observed in cases with higher proportions of European or African ancestry. A higher Native American ancestry was significantly associated with higher frequency of E variants (median ancestry > 23.6%, Age and place of birth adjusted OR: 3.55, 95% CI: 1.26–10.03, p = 0.01). Even further, an inverse geographic correlation between Native American ancestry and frequency of infections with AA variants was observed (ρ = −0.825, p = 0.008). Regions with higher proportion of Native American ancestry had a lower frequency of AA variants of HPV 16.ConclusionsThis study suggests replacement of AA variants by E variants of human papillomavirus 16 in cervical cancer cases with high Native American ancestry.     

我院静脉药物调配中心的建设与实施

目的 建设静脉药物调配中心(PIVAS),提高医院管理水平,保障患者用药安全.方法 对医院PIVAS的软硬件建设、管理及运行现状进行介绍,并阐述开展PIVAS的体会.结果 通过PIVAS的建设.可为患者提供高品质的输液产品.减少药品浪费,有利于职业防护.结论 建立PIVAS,有利于用药的安全、合理、经济,是现代医院药学服务的重要内容.