Journal Mobile Options
Table of Contents
Vol. 139, No. 3, 2006
Issue release date: February 2006
Int Arch Allergy Immunol 2006;139:209–216
(DOI:10.1159/000091166)

Gene-Based Single Nucleotide Polymorphisms and Linkage Disequilibrium Patterns of 29 Asthma Candidate Genes in the Chromosome 5q31–33 Region in Koreans

Ryu H.-J. · Jung H.-Y. · Park J.-S. · Ryu G.-M. · Heo J.Y. · Kim J.-J. · Moon S.-M. · Kim H.-T. · Lee J.-Y. · Koh I. · Kim J.-W. · Rho J.K. · Han B.-G. · Kim H. · Park C.-S. · Oh B. · Park C. · Lee J.-K. · Kimm K.
aNational Genome Research Institute, National Institute of Health, bMacrogen Co., Seoul, and cGenome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Hospital, Gyeonggi-Do, Korea

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Background and Methods: Numerous genetic studies have mapped asthma susceptibility genes to a region on chromosome 5q31–33 in several populations. This region contains a cluster of cytokines and other immune-related genes important in immune response. In the present study, to determine the genetic variations and patterns of linkage disequilibrium (LD), we resequenced all the exons and promoter regions of the 29 asthma candidate genes in the chromosome 5q31–33 region. Results: We identified a total of 314 genetic variants, including 289 single nucleotide polymorphisms (SNPs), 22 insertion/deletion polymorphisms and 3 microsatellites. Standardized variance data for allele frequency revealed substantial differences in SNP allele frequencies among different ethnic groups. Interestingly, significant ethnic differences were observed mainly in intron SNPs. LD block analysis using 174 common SNPs with a frequency of >10% disclosed strong LD within most candidate genes. No significant LD was observed across genes, except for one LD block (CD14-IK block). Gene-based haplotype analyses showed that 1–5 haplotype-tagging SNPs may be used to define the six or fewer common haplotypes with a frequency of >5%, regardless of the number of SNPs. Conclusion: Overall, our results provide useful information for the identification of immune-mediated disease genes in the chromosome 5q31–33 region, as well as valuable evidence for gene-based haplotype analysis in disease association studies.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Weiss KM: In search of human variation. Genome Res 1998;8:691–697.
  2. Pritchard JK, Przeworski M: Linkage disequilibrium in humans: models and data. Am J Hum Genet 2001;69:1–14.
  3. Olivier M, Bustos VI, Levy MR, Smick GA, Moreno I, Bushard JM, Almendras AA, Sheppard K, Zierten DL, Aggarwal A, Carlson CS, Foster BD, Vo N, Kelly L, Liu X, Cox DR: Complex high-resolution linkage disequilibrium and haplotype patterns of single-nucleotide polymorphisms in 2.5 Mb of sequence on human chromosome 21. Genomics 2001;78:64–72.
  4. Nickerson DA, Whitehurst C, Boysen C, Charmley P, Kaiser R, Hood L: Identification of clusters of biallelic polymorphic sequence-tagged sites (pSTSs) that generate highly informative and automatable markers for genetic linkage mapping. Genomics 1992;12:377–387.
  5. Johnson GC, Esposito L, Barratt BJ, Smith AN, Heward J, Di Genova G, Ueda H, Cordell HJ, Eaves IA, Dudbridge F, Twells RC, Payne F, Hughes W, Nutland S, Stevens H, Carr P, Tuomilehto-Wolf E, Tuomilehto J, Gough SC, Clayton DG, Todd JA: Haplotype tagging for the identification of common disease genes. Nat Genet 2001;29:233–237.
  6. Grunig G, Warnock M, Wakil AE, Venkayya R, Brombacher F, Rennick DM, Sheppard D, Mohrs M, Donaldson DD, Locksley RM, Corry DB: Requirement for IL-13 independently of IL-4 in experimental asthma. Science 1998;282:2261–2263.
  7. Mansur AH, Bishop DT, Markham AF, Britton J, Morrison JF: Association study of asthma and atopy traits and chromosome 5q cytokine cluster markers. Clin Exp Allergy 1998;28:141–150.
  8. Kauppi P, Lindblad-Toh K, Sevon P, Toivonen HT, Rioux JD, Villapakkam A, Laitinen LA, Hudson TJ, Kere J, Laitinen T: A second-generation association study of the 5q31 cytokine gene cluster and the interleukin-4 receptor in asthma. Genomics 2001;77:35–42.
  9. Rioux JD, Daly MJ, Silverberg MS, Lindblad K, Steinhart H, Cohen Z, Delmonte T, Kocher K, Miller K, Guschwan S, Kulbokas EJ, O’Leary S, Winchester E, Dewar K, Green T, Stone V, Chow C, Cohen A, Langelier D, Lapointe G, Gaudet D, Faith J, Branco N, Bull SB, McLeod RS, Griffiths AM, Bitton A, Greenberg GR, Lander ES, Siminovitch KA, Hudson TJ: Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet 2001;29:223–228.
  10. Lee JK, Park C, Kimm K, Rutherford MS: Genome-wide multilocus analysis for immune-mediated complex diseases. Biochem Biophys Res Commun 2002;295:771–773.
  11. Rozen S, Skaletsky H: Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 2000;132:365–386.
  12. Nickerson DA, Tobe VO, Taylor SL: PolyPhred: automating the detection and genotyping of single nucleotide substitutions using fluorescence-based resequencing. Nucleic Acids Res 1997;25:2745–2751.
  13. Qin ZS, Niu T, Liu JS: Partition-ligation-expectation-maximization algorithm for haplotype inference with single-nucleotide polymorphisms. Am J Hum Genet 2002;71:1242– 1247.
  14. Sebastiani P, Lazarus R, Weiss ST, Kunkel LM, Kohane IS, Ramoni MF: Minimal haplotype tagging. Proc Natl Acad Sci USA 2003;100:9900–9905.
  15. Tsunoda T, Lathrop GM, Sekine A, Yamada R, Takahashi A, Ohnishi Y, Tanaka T, Nakamura Y: Variation of gene-based SNPs and linkage disequilibrium patterns in the human genome. Hum Mol Genet 2004;13:1623–1632.
  16. Lewontin RC: The detection of linkage disequilibrium in molecular sequence data. Genetics 1995;140:377–388.
  17. Goddard KA, Hopkins PJ, Hall JM, Witte JS: Linkage disequilibrium and allele-frequency distributions for 114 single-nucleotide polymorphisms in five populations. Am J Hum Genet 2000;66:216–234.
  18. Kruglyak L, Nickerson DA: Variation is the spice of life. Nat Genet 2001;27:234–236.
  19. Ioannidis JPA, Ntzani EE, Trikalinos TA: ‘Racial’ differences in genetic effects for complex diseases. Nat Genet 2004;36:1312–1318.
  20. Lee JK, Kim HT, Cho SM, Kim KH, Jin HJ, Ryu GM, Oh B, Park C, Kimm K, Jo SA, Jung SC, Kim S, In SM, Lee JE, Jo I: Characterization of 458 single nucleotide polymorphisms of disease candidate genes in the Korean population. J Hum Genet 2003;48:213–216.
  21. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet 1999;22:231–238.
  22. Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A: Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet 1999;22:239–247.
  23. Rangan P, Masquida B, Westhof E, Woodson SA: Assembly of core helices and rapid tertiary folding of a small bacterial group I ribozyme. Proc Natl Acad Sci USA 2003;100:1574–1579.
  24. Dawson E, Abecasis GR, Bumpstead S, Chen Y, Hunt S, Beare DM, Pabial J, Dibling T, Tinsley E, Kirby S, Carter D, Papaspyridonos M, Livingstone S, Ganske R, Lohmussaar E, Zernant J, Tonisson N, Remm M, Magi R, Puurand T, Vilo J, Kurg A, Rice K, Deloukas P, Mott R, Metspalu A, Bentley DR, Cardon LR, Dunham I: A first-generation linkage disequilibrium map of human chromosome 22. Nature 2002;418:544–548.
  25. Phillips MS, Lawrence R, Sachidanandam R, Morris AP, Balding DJ, Donaldson MA, Studebaker JF, Ankener WM, Alfisi SV, Kuo FS, Camisa AL, Pazorov V, Scott KE, Carey BJ, Faith J, Katari G, Bhatti HA, Cyr JM, Derohannessian V, Elosua C, Forman AM, Grecco NM, Hock CR, Kuebler JM, Lathrop JA, Mockler MA, Nachtman EP, Restine SL, Varde SA, Hozza MJ, Gelfand CA, Broxholme J, Abecasis GR, Boyce-Jacino MT, Cardon LR: Chromosome-wide distribution of haplotype blocks and the role of recombination hot spots. Nat Genet 2003;33:382–387.
  26. Daly MJ, Rioux JD, Schaffner SF, Hudson TJ, Lander ES: High-resolution haplotype structure in the human genome. Nat Genet 2001;29:229–232.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50