Current practices and future trends in cockroach allergen immunotherapy

Purpose of review: This review evaluates the current modes of allergen-specific immunotherapy for cockroach allergens, in terms of clinical outcomes and explores future trends in the research and development needed for a more targeted cockroach immunotherapy approach with the best efficacy and minimum adverse effects. Summary: Cockroach allergy is an important risk factor for allergic rhinitis in the tropics, that disproportionately affects children and young adults and those living in poor socio-economic environments. Immunotherapy would provide long-lasting improvement in quality of life, with reduced medication intake. However, the present treatment regime is long and has a risk of adverse effects. In addition, cockroach does not seem to have an immuno-dominant allergen, that has been traditionally used to treat allergies from other sources. Future trends of cockroach immunotherapy involve precision diagnosis, to correctly identify the offending allergen. Next, precision immunotherapy with standardized allergens, which have been processed in a way that maintains an immunological response without allergic reactions. This approach can be coupled with modern adjuvants and delivery systems that promote a Th1/Treg environment, thereby modulating the immune response away from the allergenic response

Evaluating the transferability of Hapmap SNPs to a Singapore Chinese population

<p>Abstract</p> <p>Background</p> <p>The International Hapmap project serves as a valuable resource for human genome variation data, however its applicability to other populations has yet to be exhaustively investigated. In this paper, we use high density genotyping chips and resequencing strategies to compare the Singapore Chinese population with the Hapmap populations. First we compared 1028 and 114 unrelated Singapore Chinese samples genotyped using the Illumina Human Hapmap 550 k chip and Affymetrix 500 k array respectively against the 270 samples from Hapmap. Secondly, data from 20 candidate genes on 5q31-33 resequenced for an asthma candidate gene based study was also used for the analysis.</p> <p>Results</p> <p>A total of 237 SNPs were identified through resequencing of which only 95 SNPs (40%) were in Hapmap; however an additional 56 SNPs (24%) were not genotyped directly but had a proxy SNP in the Hapmap. At the genome-wide level, Singapore Chinese were highly correlated with Hapmap Han Chinese with correlation of 0.954 and 0.947 for the Illumina and Affymetrix platforms respectively with deviant SNPs randomly distributed within and across all chromosomes.</p> <p>Conclusions</p> <p>The high correlation between our population and Hapmap Han Chinese reaffirms the applicability of Hapmap based genome-wide chips for GWA studies. There is a clear population signature for the Singapore Chinese samples and they predominantly resemble the southern Han Chinese population; however when new migrants particularly those with northern Han Chinese background were included, population stratification issues may arise. Future studies needs to address population stratification within the sample collection while designing and interpreting GWAS in the Chinese population.</p

Characterizing haploinsufficiency of SHELL gene to improve fruit form prediction in introgressive hybrids of oil palm

The fundamental trait in selective breeding of oil palm (Eleais guineensis Jacq.) is the shell thickness surrounding the kernel. The monogenic shell thickness is inversely correlated to mesocarp thickness, where the crude palm oil accumulates. Commercial thin-shelled tenera derived from thick-shelled dura × shell-less pisifera generally contain 30% higher oil per bunch. Two mutations, shᴹᴾᴼᴮ (M1) and shAVROS (M2) in the SHELL gene – a type II MADS-box transcription factor mainly present in AVROS and Nigerian origins, were reported to be responsible for different fruit forms. In this study, we have tested 1,339 samples maintained in Sime Darby Plantation using both mutations. Five genotype-phenotype discrepancies and eight controls were then re-tested with all five reported mutations (shAVROS, shᴹᴾᴼᴮ, shᴹᴾᴼᴮ², shᴹᴾᴼᴮ ³ and shᴹᴾᴼᴮ⁴) within the same gene. The integration of genotypic data, pedigree records and shell formation model further explained the haploinsufficiency effect on the SHELL gene with different number of functional copies. Some rare mutations were also identified, suggesting a need to further confirm the existence of cis-compound mutations in the gene. With this, the prediction accuracy of fruit forms can be further improved, especially in introgressive hybrids of oil palm. Understanding causative variant segregation is extremely important, even for monogenic traits such as shell thickness in oil palm

A practical genome-enabled legitimacy assay for oil palm breeding and seed production

Background: Legitimacy in breeding and commercial crop production depends on optimised protocols to ensure purity of crosses and correct field planting of material. In oil palm, the presence of three fruit forms permits these assumptions to be tested, although only after field planting. The presence of incorrect fruit forms in a cross is a clear sign of illegitimacy. Given that tenera forms produce 30% more oil for the same weight of fruit as dura, the presence of low levels of dura contamination can have major effect during the economic lifespan of an oil palm, which is around 25 years. We evaluated two methods for legitimacy test 1) The use of SHELL markers to the gene that determines the shell-thickness trait 2) The use of SNP markers, to determine the legitimacy of the cross

Crystal Structure of Der f 7, a Dust Mite Allergen from Dermatophagoides farinae

10.1371/journal.pone.0044850PLoS ONE79

Characterizing haploinsufficiency of SHELL gene to improve fruit form prediction in introgressive hybrids of oil palm

The fundamental trait in selective breeding of oil palm (Eleais guineensis Jacq.) is the shell thickness surrounding the kernel. The monogenic shell thickness is inversely correlated to mesocarp thickness, where the crude palm oil accumulates. Commercial thin-shelled tenera derived from thick-shelled dura × shell-less pisifera generally contain 30% higher oil per bunch. Two mutations, shᴹᴾᴼᴮ (M1) and shAVROS (M2) in the SHELL gene – a type II MADS-box transcription factor mainly present in AVROS and Nigerian origins, were reported to be responsible for different fruit forms. In this study, we have tested 1,339 samples maintained in Sime Darby Plantation using both mutations. Five genotype-phenotype discrepancies and eight controls were then re-tested with all five reported mutations (shAVROS, shᴹᴾᴼᴮ, shᴹᴾᴼᴮ², shᴹᴾᴼᴮ ³ and shᴹᴾᴼᴮ⁴) within the same gene. The integration of genotypic data, pedigree records and shell formation model further explained the haploinsufficiency effect on the SHELL gene with different number of functional copies. Some rare mutations were also identified, suggesting a need to further confirm the existence of cis-compound mutations in the gene. With this, the prediction accuracy of fruit forms can be further improved, especially in introgressive hybrids of oil palm. Understanding causative variant segregation is extremely important, even for monogenic traits such as shell thickness in oil palm

Multiplexed genotyping of ABC transporter polymorphisms with the Bioplex suspension array

We have developed and validated a consolidated bead-based genotyping platform, the Bioplex suspension array for simultaneous detection of multiple single nucleotide polymorphisms (SNPs) of the ATP-binding cassette transporters. Genetic polymorphisms have been known to influence therapeutic response and risk of disease pathologies. Genetic screening for therapeutic and diagnostic applications thus holds great promise in clinical management. The allele-specific primer extension (ASPE) reaction was used to assay 22 multiplexed SNPs for eight subjects. Comparison of the microsphere-based ASPE assay results to sequencing results showed complete concordance in genotype assignments. The Bioplex suspension array thus proves to be a reliable, cost-effective and high-throughput technological platform for genotyping. It can be easily adapted to customized SNP panels for specific applications involving large-scale mutation screening of clinically relevant markers

Validation of pooled genotyping on the Affymetrix 500 k and SNP6.0 genotyping platforms using the polynomial-based probe-specific correction

10.1186/1471-2156-10-82BMC Genetics10-BGME

Variation in Uteroglobin-Related Protein 1 (UGRP1) gene is associated with Allergic Rhinitis in Singapore Chinese

<p>Abstract</p> <p>Background</p> <p>Uteroglobin-Related Protein 1 (<it>UGRP1</it>) is a secretoglobulin protein which has been suggested to play a role in lung inflammation and allergic diseases. UGRP1 has also been shown to be an important pneumoprotein, with diagnostic potential as a biomarker of lung damage. Previous genetic studies evaluating the association between variations on <it>UGRP1 </it>and allergic phenotypes have yielded mixed results. The aim of this present study was to identify genetic polymorphisms in <it>UGRP1 </it>and investigate if they were associated with asthma and allergic rhinitis in the Singapore Chinese population.</p> <p>Methods</p> <p>Resequencing of the <it>UGRP1 </it>gene was conducted on 40 randomly selected individuals from Singapore of ethnic Chinese origin. The polymorphisms identified were then tagged and genotyped in a population of 1893 Singapore Chinese individuals. Genetic associations were evaluated in this population comparing 795 individuals with allergic rhinitis, 718 with asthma (of which 337 had both asthma and allergic rhinitis) and 717 healthy controls with no history of allergy or allergic diseases.</p> <p>Results</p> <p>By resequencing the <it>UGRP1 </it>gene within our population, we identified 11 novel and 16 known single nucleotide polymorphisms (SNPs). TagSNPs were then genotyped, revealing a significant association between rs7726552 and allergic rhinitis (Odds Ratio: 0.81, 95% Confidence Interval: 0.66-0.98, P = 0.039). This association remained statistically significant when it was analyzed genotypically or when stratified according to haplotypes. When variations on <it>UGRP1 </it>were evaluated against asthma, no association was observed.</p> <p>Conclusion</p> <p>This study documents the association between polymorphisms in <it>UGRP1 </it>and allergic rhinitis, suggesting a potential role in its pathogenesis.</p

Immunological corollary of the pulmonary mycobiome in bronchiectasis:The Cameb study

Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a “research priorities” consensus statement for bronchiectasis. Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S–28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes. The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus, Cryptococcus and Clavispora. Aspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus-associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations. The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus-associated disease should be considered even in apparently stable patients.MOE (Min. of Education, S’pore)NMRC (Natl Medical Research Council, S’pore)Published versio