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Applications of Molecular Genetics to the Study of Asthma

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Molecular Genetics of Asthma

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1434))

Abstract

Asthma is a multifactorial disease. This fact, associated to the diversity of asthma phenotypes, has made difficult to obtain a clear pattern of inheritance. With the huge development of molecular genetics technologies, candidate gene studies are giving way to different types of studies from the genomic point of view.

These approaches are allowing the identification of several genes associated with asthma. However, in these studies, there are some conflicting results between different populations and there is still a lack of knowledge about the actual influence of the gene variants. Some confounding factors are, among others, the inappropriate sample size, population stratification, differences in the classification of the phenotypes, or inadequate coverage of the genes.

To confirm the real effect of the reported associations, it is necessary to consider both the genetic and environmental factors and perform functional studies that explain the molecular mechanisms mediating between the emergence of gene variants and the development of the disease.

The development of experimental techniques opens a new horizon that allows the identification of major genetic factors of susceptibility to asthma. The resulting classification of the population groups based on their genetic characteristics, will allow the application of specific and highly efficient treatments.

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References

  1. Call for Global Action on Chronic Respiratory Diseases organized by the World Health Organization and the European Federation of Allergy and Airways Diseases (Rome, 11 June 2009). http://www.efanet.org/enews/press.html/, http://www.who.int/respiratory/gard/en/

  2. Mayo O (2007) The rise and fall of the common disease-common variant (CD-CV) hypothesis: how the sickle cell disease paradigm led us all astray (or did it?). Twin Res Hum Genet 10(6):793–804

    Article  PubMed  Google Scholar 

  3. International HapMap Consortium, Frazer KA, Ballinger DG, Cox DR et al (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449(7164):851–861

    Article  Google Scholar 

  4. Barrett JC, Fry B, Maller J et al (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 15(2):263–265

    Article  Google Scholar 

  5. Wang DG, Fan JB, Siao CJ et al (1998) Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science 280:1077–1082

    Article  CAS  PubMed  Google Scholar 

  6. Saccone SF, Bierut LJ, Chesler EJ et al (2009) Supplementing high-density SNP microarrays for additional coverage of disease-related genes: addiction as a paradigm. PLoS One 4(4):e5225. doi:10.1371/journal.pone.0005225

    Article  PubMed  PubMed Central  Google Scholar 

  7. Moffatt MF, Kabesch M, Liang L et al (2007) Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448(7152):470–473

    Article  CAS  PubMed  Google Scholar 

  8. Galanter J, Choudhry S, Eng C et al (2008) ORMDL3 gene is associated with asthma in three ethnically diverse populations. Am J Respir Crit Care Med 177(11):1194–1200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hirota T, Harada M, Sakashita M et al (2008) Genetic polymorphism regulating ORM1-like 3 (Saccharomyces cerevisiae) expression is associated with childhood atopic asthma in a Japanese population. J Allergy Clin Immunol 121(3):769–770

    Article  CAS  PubMed  Google Scholar 

  10. Leung TF, Sy HY, Ng MC et al (2009) Asthma and atopy are associated with chromosome 17q21 markers in Chinese children. Allergy 64(4):621–628

    Article  CAS  PubMed  Google Scholar 

  11. Cantero-Recasens G, Fandos C, Rubio-Moscardo F et al (2010) The asthma-associated ORMDL3 gene product regulates endoplasmic reticulum-mediated calcium signaling and cellular stress. Hum Mol Genet 19(1):111–121

    Article  CAS  PubMed  Google Scholar 

  12. Breslow DK, Collins SR, Bodenmiller B et al (2010) Orm family proteins mediate sphingolipid homeostasis. Nature 463(7284):1048–1053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Verlaan DJ, Berlivet S, Hunninghake GM et al (2009) Allele-specific chromatin remodeling in the ZPBP2/GSDMB/ORMDL3 locus associated with the risk of asthma and autoimmune disease. Am J Hum Genet 85(3):377–393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. McGovern DP, Gardet A, Törkvist L et al (2010) Genome-wide association identifies multiple ulcerative colitis susceptibility loci. Nat Genet 42(4):332–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Barrett JC, Clayton DG, Concannon P et al (2009) Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 41(6):703–707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sleiman PM, Flory J, Imielinski M et al (2010) Variants of DENND1B associated with asthma in children. N Engl J Med 362:36–44

    Article  CAS  PubMed  Google Scholar 

  17. Moffatt MF, Gut IG, Demenais F et al (2010) A large-scale, consortium-based genome wide association study of asthma. N Engl J Med 363(13):1211–1221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hirota T, Takahashi A, Kubo M et al (2011) Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. Nat Genet 43:893–896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Repapi E, Sayers I, Wain LV et al (2010) Genome-wide association study identifies five loci associated with lung function. Nat Genet 42:36–44

    Article  CAS  PubMed  Google Scholar 

  20. Hancock DB, Eijgelsheim M, Wilk JB et al (2010) Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat Genet 42:45–52

    Article  CAS  PubMed  Google Scholar 

  21. Bernstein DI (2011) Genetics of occupational asthma. Curr Opin Allergy Clin Immunol 11(2):86–89

    Article  CAS  PubMed  Google Scholar 

  22. Torgerson DG, Ampleford EJ, Chiu GY et al (2011) Meta analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet 43:887–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ferreira MA, Matheson MC, Duffy DL et al (2011) Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet 378:1006–1014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Li X, Howard TD, Zheng SL et al (2010) Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DRDQ regions. J Allergy Clin Immunol 125:328–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Weidinger S, Gieger C, Rodriguez E et al (2008) Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus. PLoS Genet 4(8):e1000166

    Article  PubMed  PubMed Central  Google Scholar 

  26. Binia A, Kabesch M (2012) Respiratory medicine – genetic base for allergy and asthma. Swiss Med Wkly 142:1–11

    Google Scholar 

  27. Wan YI, Strachan DP, Evans DM et al (2011) A genome-wide association study to identify genetic determinants of atopy in subjects from the United Kingdom. J Allergy Clin Immunol 127(1):223–231

    Article  CAS  PubMed  Google Scholar 

  28. Ramasamy A, Curjuric I, Coin LJ et al (2011) A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. J Allergy Clin Immunol 128:996–1005

    Article  CAS  PubMed  Google Scholar 

  29. Rothenberg ME, Spergel JM, Sherrill JD et al (2010) Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet 42:289–291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Esparza-Gordillo J, Weidinger S, Fölster-Holst R et al (2009) A common variant on chromosome 11q13 is associated with atopic dermatitis. Nat Genet 41:596–601

    Article  CAS  PubMed  Google Scholar 

  31. Sun LD, Xiao FL, Li Y et al (2011) Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population. Nat Genet 43:690–694

    Article  CAS  PubMed  Google Scholar 

  32. Paternoster L, Standl M, Chen CM et al (2011) Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat Genet 44:187–192

    Article  PubMed  PubMed Central  Google Scholar 

  33. Hirota T, Takahashi A, Kubo M et al (2012) Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nat Genet 44:1222–1226

    Article  CAS  PubMed  Google Scholar 

  34. Ober C, Tan Z, Sun Y et al (2008) Effect of variation in CHI3L1 on serum YKL-40 level, asthma risk, and lung function. N Engl J Med 358:1682–1691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wilk JB, Chen TH, Gottlieb DJ et al (2009) A genome-wide association study of pulmonary function measures in the Framingham Heart Study. PLoS Genet 5:e1000429

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wilk JB, Chen TH, Gottlieb DJ et al (2009) A genome-wide association study of pulmonary function measures in the Framingham Heart Study. PLoS Genet 5(3):e1000429. doi:10.1371/journal.pgen.1000429

    Article  PubMed  PubMed Central  Google Scholar 

  37. Sanger F, Air GM, Barrell BG et al (1977) Nucleotide sequence of bacteriophage phi X174 DNA. Nature 24:687–695

    Article  Google Scholar 

  38. Buermans HP, den Dunnen JT (2014) Next generation sequencing technology: advances and applications. Biochim Biophys Acta 1842(10):1932–1941

    Article  CAS  PubMed  Google Scholar 

  39. Metzker ML (2005) Emerging technologies in DNAsequencing. Genome Res 15:1767–1776

    Article  CAS  PubMed  Google Scholar 

  40. Tomkinson AE, Vijayakumar S, Pascal JM et al (2006) DNA ligases: structure, reaction mechanism, and function. Chem Rev 106:687–699

    Article  CAS  PubMed  Google Scholar 

  41. Ronaghi M, Uhlén M, Nyrén P (1998) A sequencing method based on real-time pyrophosphate. Science 281:363–365

    Article  CAS  PubMed  Google Scholar 

  42. Ronaghi M, Karamohamed S, Pettersson B et al (1996) Real-time DNA sequencing using detection of pyrophosphate release. Anal Biochem 242:84–89

    Article  CAS  PubMed  Google Scholar 

  43. Margulies M, Egholm M, Altman WE et al (2005) Genome sequencing in micro fabricated high-density picolitre reactors. Nature 437:376–380

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Bentley DR, Balasubramanian S, Swerdlow HP et al (2008) Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456:53–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Dohm JC, Lottaz C, Borodina T et al (2008) Substantial biases in ultra-short read data sets fromhigh-throughput DNA sequencing. Nucleic Acids Res 36:e105

    Article  PubMed  PubMed Central  Google Scholar 

  46. Hillier LW, Marth GT, Quinlan AR et al (2008) Whole-genome sequencing andvariant discovery in C. elegans. Nat Methods 5:83–188

    Article  Google Scholar 

  47. Harismendy O, Ng PC, Strausberg RL et al (2009) Evaluation of next generationsequencing platforms for population targetedsequencing studies. Genome Biol 10(3):R32. doi:10.1186/gb-2009-10-3-r32, Epub 2009 Mar 27

    Article  PubMed  PubMed Central  Google Scholar 

  48. Valouev A, Ichikawa J, Tonthat T et al (2008) A high-resolution, nucleosomeposition map of C. elegans reveals a lack of universalsequence-dictated positioning. Genome Res 18:1051–1063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Chen G, Wang C, Shi T (2011) Overview of available methods for diverse RNA-Seq data analyses. Sci China Life Sci 54(12):1121–1128

    Article  CAS  PubMed  Google Scholar 

  50. Qi YX, Liu YB, Rong WH (2011) RNA-Seq and its applications: a new technology for transcriptomics. Yi Chuan 33(11):1191–1202

    Article  CAS  PubMed  Google Scholar 

  51. Yick CY, Zwinderman AH, Kunst PW et al (2013) Transcriptome sequencing (RNA-Seq) of human endobronchial biopsies: asthma versus controls. Eur Respir J 42(3):662–670

    Article  CAS  PubMed  Google Scholar 

  52. Pascual M, Roa S, García-Sánchez A et al (2014) Genome-wide expression profiling of B lymphocytes reveals IL4R increase in allergic asthma. J Allergy Clin Immunol 134(4):972–975

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This work was supported by a grant of the Junta de Castilla y León ref BIO/SA73/15.

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Correspondence to Catalina S. Sanz-Lozano .

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Sanz-Lozano, C.S., García-Solaesa, V., Davila, I., Isidoro-García, M. (2016). Applications of Molecular Genetics to the Study of Asthma. In: Isidoro García, M. (eds) Molecular Genetics of Asthma. Methods in Molecular Biology, vol 1434. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3652-6_1

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  • DOI: https://doi.org/10.1007/978-1-4939-3652-6_1

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  • Publisher Name: Humana Press, New York, NY

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