eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
Current issue Archive Manuscripts accepted About the journal Supplements Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
3/2017
vol. 68
 
Share:
Share:
more
 
 
abstract:
Original paper

Massively parallel targeted resequencing reveals novel genetic variants associated with aspergillosis in paediatric patients with haematological malignancies

Katarzyna Skonieczna, Jan Styczyński, Anna Krenska, Piotr Stawiński, Rafał Płoski, Katarzyna Derwich, Wanda Badowska, Mariusz Wysocki, Tomasz Grzybowski

Pol J Pathol 2017; 68 (3): 210-217
Online publish date: 2017/11/30
View full text
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
This study aimed to find novel genetic variants of susceptibility to aspąergillosis in paediatric patients with haematological malignancies. Complete sequences of fifteen genes of human innate immunity (CCL2, CCR2, CD209, CLEC6A, CLEC7A and ten TLR genes) were studied in 40 patients diagnosed with haematological disorders (20 unaffected and 20 affected by aspergillosis). All samples were sequenced with MiSeq (Illumina) and 454 (Roche Diagnostics) technologies. Statistical significance of the differences between studied groups was determined using the two-tailed Fisher’s exact test. Sixty variants of potential importance were identified, the vast majority of which are located in non-coding parts of the targeted genes. At the threshold of p < 0.000005, one intergenic (TLR2 rs4585282) and one intronic variant (CLEC6A rs12099687) were found significant between the case and control groups for genotype and allele frequencies, respectively. Rs12099687 in CLEC6A was predicted to constitute an alternative isoform or cryptic splice site, which potentially changes activity of the Dectin-2 protein. Overall, we assume that the two strongest associations reported in this study are expected to be reproducible even in the absence of other evidence, while another twelve associations may be strong enough to justify additional research in larger cohorts.
keywords:

aspergillosis, children, human innate immunity genes, massively parallel sequencing, SNP

references:
Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008; 46: 327-360.
Morgan JE, Hassan H, Cockle JV, et al. Critical review of current clinical practice guidelines for antifungal therapy in paediatric haematology and oncology. Support Care Cancer 2017; 25: 221-228.
Herbrecht R, Bories P, Moulin JC, Ledoux MP, Letscher-Bru V. Risk stratification for invasive aspergillosis in immunocompromised patients. Ann N Y Acad Sci 2012; 1272: 23-30.
Schleicher J, Conrad T, Gustafsson M, et al. Facing the challenges of multiscale modelling of bacterial and fungal pathogen-host interactions. Brief Funct Genomics 2017; 16: 57-69.
Dix A, Czakai K, Springer J, et al. Genome-Wide Expression Profiling Reveals S100B as Biomarker for Invasive Aspergillosis. Front Microbiol 2016; 7: 320.
Wójtowicz A, Bochud PY. Host genetics of invasive Aspergillus and Candida infections. Semin Immunopathol 2015; 37: 173-186.
Lupia¼ez CB, Villaescusa MT, Carvalho A, et al. Common Genetic Polymorphisms within NFB-Related Genes and the Risk of Developing Invasive Aspergillosis. Front Microbiol 2016; 7: 1243.
Pana ZD, Farmaki E, Roilides E. Host genetics and opportunistic fungal infections. Clin Microbiol Infect 2014; 20: 1254-1264.
Auer PL, Lettre G. Rare variant association studies: considerations, challenges and opportunities. Genome Med 2015; 7: 16.
Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25: 1754-1760.
McKenna A, Hanna M, Banks E, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 2010; 20: 1297-1303.
Sherry ST, Ward MH, Kholodov M, et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 2001; 29: 308-311.
1000 Genomes Project Consortium, Auton A, Brooks LD, et al.. A global reference for human genetic variation. Nature 2015; 526: 68-74.
Beck T, Hastings RK, Gollapudi S, et al. GWAS Central: a comprehensive resource for the comparison and interrogation of genome-wide association studies. Eur J Hum Genet 2014; 22: 949-952.
Yates A, Akanni W, Amode MR, et al. Ensembl 2016. Nucleic Acids Res 2016 44: D710-D716.
Manly KF. Reliability of statistical associations between genes and disease. Immunogenetics 2005, 57: 549-558.
Wang M, Marín A. Characterization and prediction of alternative splice sites. Gene 2006; 366: 219-227.
Overton NL, Denning DW, Bowyer P, Simpson A. Genetic susceptibility to allergic bronchopulmonary aspergillosis in asthma: a genetic association study. Allergy Asthma Clin Immunol 2016; 12: 47.
Bochud PY, Chien JW, Marr KA, et al. Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N Engl J Med 2008; 359: 1766-1777.
Bank S, Andersen PS, Burisch J, et al. Associations between functional polymorphisms in the NFB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease. Pharmacogenomics J 2014; 14: 526-534.
Bharti D, Kumar A, Mahla RS, et al. The role of TLR9 polymorphism in susceptibility to pulmonary tuberculosis. Immunogenetics 2014; 66: 675-681.
He D, Tao S, Guo S, et al. Interaction of TLR-IFN and HLA polymorphisms on susceptibility of chronic HBV infection in Southwest Han Chinese. Liver Int 2015; 35: 1941-1949.
Karody V, Reese S, Kumar N, et al. A toll-like receptor 9 (rs352140) variant is associated with placental inflammation in newborn infants. J Matern Fetal Neonatal Med 2016; 29: 2210-2216.
Lee J, Kim YJ, Lee J. Gene-set association tests for next-generation sequencing data. Bioinformatics 2016; 32: i611-i619.
Paradowska E, Jabłońska A, Studzińska M, et al. TLR9 -1486T/C and 2848C/T SNPs Are Associated with Human Cytomegalovirus Infection in Infants. PLoS One 2016; 11: e0154100.
Yoon S, Kang BW, Park SY, et al. Prognostic relevance of genetic variants involved in immune checkpoints in patients with colorectal cancer. J Cancer Res Clin Oncol 2016; 142: 1775-1780.
Sunakawa Y, Stintzing S, Cao S, et al. Variations in genes regulating tumor-associated macrophages (TAMs) to predict outcomes of bevacizumab-based treatment in patients with metastatic colorectal cancer: results from TRIBE and FIRE3 trials. Ann Oncol 2015; 26: 2450-2456.
Traks T, Keermann M, Karelson M, et al. Polymorphisms in Toll-like receptor genes are associated with vitiligo. Front Genet 2015; 6: 278.
Velez DR, Wejse C, Stryjewski ME, et al. Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans. Hum Genet 2010; 127: 65-73.
Dannemann M, Andrés AM, Kelso J. Introgression of Neandertal- and Denisovan-like haplotypes contributes to adaptive variation in human toll-like receptors. Am J Hum Genet 2016; 98: 22-33.
Hubé F, Francastel C. Mammalian introns: when the junk generates molecular diversity. Int J Mol Sci, 2015; 16: 4429-4452.
Loures FV, Röhm M, Lee CK, et al. Recognition of Aspergillus fumigatus hyphae by human plasmacytoid dendritic cells is mediated by dectin-2 and results in formation of extracellular traps. PLoS Pathog 2015; 11: e1004643.
Krieg AM. Toll-like receptor 9 (TLR9) agonists in the treatment of cancer. Oncogene 2008; 27: 161-167.
Sainz J, Lupiá¼ez CB, Segura-Catena J, et al. Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary Aspergillosis infection. PLoS One 2012; 7: e32273.
FEATURED PRODUCTS
Quick links
© 2018 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe