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Theoretical and Applied Genetics

, Volume 124, Issue 1, pp 111–124 | Cite as

Effect of population size and unbalanced data sets on QTL detection using genome-wide association mapping in barley breeding germplasm

  • Hongyun Wang
  • Kevin P. Smith
  • Emily Combs
  • Tom Blake
  • Richard D. Horsley
  • Gary J. MuehlbauerEmail author
Original Paper

Abstract

Over the past two decades many quantitative trait loci (QTL) have been detected; however, very few have been incorporated into breeding programs. The recent development of genome-wide association studies (GWAS) in plants provides the opportunity to detect QTL in germplasm collections such as unstructured populations from breeding programs. The overall goal of the barley Coordinated Agricultural Project was to conduct GWAS with the intent to couple QTL detection and breeding. The basic idea is that breeding programs generate a vast amount of phenotypic data and combined with cheap genotyping it should be possible to use GWAS to detect QTL that would be immediately accessible and used by breeding programs. There are several constraints to using breeding program-derived phenotype data for conducting GWAS namely: limited population size and unbalanced data sets. We chose the highly heritable trait heading date to study these two variables. We examined 766 spring barley breeding lines (panel #1) grown in balanced trials and a subset of 384 spring barley breeding lines (panel #2) grown in balanced and unbalanced trials. In panel #1, we detected three major QTL for heading date that have been detected in previous bi-parental mapping studies. Simulation studies showed that population sizes greater than 384 individuals are required to consistently detect QTL. We also showed that unbalanced data sets from panel #2 can be used to detect the three major QTL. However, unbalanced data sets resulted in an increase in the false-positive rate. Interestingly, one-step analysis performed better than two-step analysis in reducing the false-positive rate. The results of this work show that it is possible to use phenotypic data from breeding programs to detect QTL, but that careful consideration of population size and experimental design are required.

Keywords

Quantitative Trait Locus Single Nucleotide Polymorphism Marker Major Quantitative Trait Locus Fusarium Head Blight Resistance Quantitative Trait Locus Detection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This research was supported by USDA-CSREES-NRI Grant No. 2006-55606-16722 and USDA-NIFA Grant No. 2009-85606-05701, “Barley Coordinated Agricultural Project: Leveraging Genomics, Genetics, and Breeding for Gene Discovery and Barley Improvement”.

Supplementary material

122_2011_1691_MOESM1_ESM.ppt (226 kb)
Supplementary material 1 (PPT 225 kb)
122_2011_1691_MOESM2_ESM.doc (94 kb)
Supplementary material 2 (DOC 94 kb)

References

  1. Beló A, Zheng P, Luck S, Shen B, Meyer DJ, Li B, Tingey S, Rafalski A (2008) Whole genome scan detects an allelic variant of fad2 associated with increased oleic acid levels in maize. Mol Genet Genomics 279:1–10PubMedCrossRefGoogle Scholar
  2. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B-Stat Methodol 57:289–300Google Scholar
  3. Bernardo R (2008) Molecular markers and selection for complex traits in plants: learning from the last 20 years. Crop Sci 48:1649–1664CrossRefGoogle Scholar
  4. Bernardo R (2010) Breeding for quantitative traits in plants, 2nd edn. Stemma Press Woodburn, MNGoogle Scholar
  5. Bradbury PJ, Zhang Z, Kroon DE, Casstevens TM, Ramdoss Y, Buckler ES (2007) TASSEL: software for association mapping of complex traits in diverse samples. Bioinformatics 23:2633–2635PubMedCrossRefGoogle Scholar
  6. Bradbury P, Parker T, Hamblin MT, Jannink JL (2011) Assessment of power and false discovery in genome-wide association studies using the BarleyCAP germplasm. Crop Sci 51:52–59CrossRefGoogle Scholar
  7. Breseghello F, Sorrells ME (2006) Association mapping of kernel size and milling quality in wheat (Triticum aestivum L.) cultivars. Genetics 172:1165–1177PubMedCrossRefGoogle Scholar
  8. Close TJ, Bhat PR, Lonardi S, Wu Y, Rostoks N, Ramsay L, Druka A, Stein N, Svensson JT, Wanamaker S, Bozdag S, Roose ML, Moscou MJ, Chao S, Varshney RK, Szucs P, Sato K, Hayes PM, Matthews DE, Kleinhofs A, Muehlbauer GJ, DeYoung J, Marshall DF, Madishetty K, Fenton RD, Condamine P, Graner A, Waugh R (2009) Development and implementation of high-throughput SNP genotyping in barley. BMC Genomics 10:582PubMedCrossRefGoogle Scholar
  9. Cockram J, White J, Zuluaga DL, Smith D, Comadran J, Macaulay M, Luo Z, Kearsey MJ, Werner P, Harrap D, Tapsell C, Liu H, Hedley PE, Stein N, Schulte D, Steuernagel B, Marshall DF, Thomas WTB, Ramsay L, Mackay I, Balding DJ, Waugh R, O’Sullivan DM, AGOUEB Consortium (2010) Genome-wide association mapping to candidate polymorphism resolution in the unsequenced barley genome. Proc Natl Acad Sci USA 107:21611–21616PubMedCrossRefGoogle Scholar
  10. Comadran J, Russell JR, Booth A, Pswarayi A, Ceccarelli S, Grando S, Stanca AM, Pecchioni N, Akar T, Al-Yassin A, Benbelkacem A, Ouabbou H, Bort J, van Eeuwijk FA, Thomas WT, Romagosa I (2011) Mixed model association scans of multi-environmental trial data reveal major loci controlling yield and yield related traits in Hordeum vulgare in Mediterranean environments. Theor Appl Genet 122:1363–1373PubMedCrossRefGoogle Scholar
  11. Condon F, Gustus C, Rasmusson DC, Smith KP (2008) Effect of advanced cycle breeding on genetic diversity in barley breeding germplasm. Crop Sci 48:1027–1036CrossRefGoogle Scholar
  12. Cuesta-Marcos A, Igartua E, Ciudad FJ, Codesal P, Russell JR, Molina-Cano JL, Moralejo M, Szucs P, Gracia MP, Lasa JM, Casas AM (2008) Heading date QTL in a spring x winter barley cross evaluated in Mediterranean environments. Mol Breed 21:455–471CrossRefGoogle Scholar
  13. Cuesta-Marcos A, Szűcs P, Close TJ, Filichkin T, Muehlbauer GJ, Smith KP, Hayes PM (2010) Genome-wide SNPs and re-sequencing of growth habit and inflorescence genes in barley: implications for association mapping in germplasm arrays varying in size and structure. BMC Genomics 11:707PubMedCrossRefGoogle Scholar
  14. Cullis B, Gogel B, Verbyla A, Thompson R (1998) Spatial analysis of multi-environment early generation variety trials. Biometrics 54:1–18CrossRefGoogle Scholar
  15. Dudley JW, Johnson GR (2009) Epistatic models improve prediction of performance in corn. Crop Sci 49:763–770CrossRefGoogle Scholar
  16. Evanno G, Regnaut S, Goudet J (2005) Detecting the number of clusters of individuals using the software STRUCTURE: a simulation study. Mol Ecol 14:2611–2620PubMedCrossRefGoogle Scholar
  17. Fan JB, Chee MS, Gunderson KL (2006) Highly parallel genomic assays. Nat Rev Genet 7:632–644PubMedCrossRefGoogle Scholar
  18. Franckowiak JD, Konishi T (2002) Early maturity 6, Eam6. Barley Genet Newsl 32:86–87Google Scholar
  19. Gaut BS, Long AD (2003) The lowdown on linkage disequilibrium. Plant Cell 15:1502–1506PubMedCrossRefGoogle Scholar
  20. Hamblin MT, Close TJ, Bhat PR, Chao S, Kling JG, Abraham KJ, Blake T, Brooks WS, Cooper B, Griffey CA, Hayes PM, Hole DJ, Horsley RD, Obert DE, Smith KP, Ullrich SE, Muehlbauer GJ, Jannink J-L (2010) Population structure and linkage disequilibrium in U.S. barley germplasm: implications for association mapping. Crop Sci 50:556–566CrossRefGoogle Scholar
  21. Holland JB, Nyquist WE, Cervantes-Martínez CT (2003) Estimating and interpreting heritability for plant breeding: an update. Plant Breed Rev 22:9–112Google Scholar
  22. Horsley RD, Schmierer D, Maier C, Kudrna D, Urrea CA, Steffenson BJ, Schwarz PB, Franckowiak JD, Green MJ, Zhang B, Kleinhofs A (2006) Identification of QTLs associated with Fusarium head blight resistance in barley accession CIho 4196. Crop Sci 46:145–156CrossRefGoogle Scholar
  23. Huang X, Wei X, Sang T, Zhao Q, Feng Q, Zhao Y, Li C, Zhu C, Lu T, Zhang Z, Li M, Fan D, Guo Y, Wang A, Wang L, Deng L, Li W, Lu Y, Weng Q, Liu K, Huang T, Zhou T, Jing Y, Li W, Lin Z, Buckler ES, Qian Q, Zhang Q, Li J, Han B (2010) Genome-wide association studies of 14 agronomic traits in rice landraces. Nat Genet 42:961–967PubMedCrossRefGoogle Scholar
  24. Khatkar MS, Nicholas FW, Collins AR, Zenger KR, Cavanagh JA, Barris W, Schnabel RD, Taylor JF, Raadsma HW (2008) Extent of genome-wide linkage disequilibrium in Australian Holstein-Friesian cattle based on a high-density SNP panel. BMC Genomics 9:187PubMedCrossRefGoogle Scholar
  25. Kraakman ATW, Niks RE, Van den Berg PMMM, Stam P, Van Eeuwijk FA (2004) Linkage disequilibrium mapping of yield and yield stability in modern spring barley cultivars. Genetics 168:435–446PubMedCrossRefGoogle Scholar
  26. Kraakman ATW, Martínez F, Mussiraliev B, Van Eeuwijk F, Niks R (2006) Linkage disequilibrium mapping of morphological, resistance, and other agronomically relevant traits in modern spring barley cultivars. Mol Breed 17:41–58CrossRefGoogle Scholar
  27. Lorenz AJ, Hamblin MT, Jannink JL, Baxter I (2010) Performance of single nucleotide polymorphisms versus haplotypes for genome-wide association analysis in barley. PloS One 5:e14079PubMedCrossRefGoogle Scholar
  28. Massman J, Cooper B, Horsley R, Neate S, Dill-Macky R, Chao S, Dong Y, Schwarz P, Muehlbauer GJ, Smith KP (2011) Genome-wide association mapping of Fusarium head blight resistance in contemporary barley breeding germplasm. Mol Breed 27:439–454CrossRefGoogle Scholar
  29. Mesfin A, Smith KP, Dill-Macky R, Evans CK, Waugh R, Gustus CD, Muehlbauer GJ (2003) Quantitative trait loci for Fusarium head blight resistance in barley detected in a two-rowed by six-rowed population. Crop Sci 43:307–318CrossRefGoogle Scholar
  30. Myles S, Peiffer J, Brown PJ, Ersoz ES, Zhang Z, Costich DE, Buckler ES (2009) Association mapping: critical considerations shift from genotyping to experimental design. Plant Cell 21:2194–2202PubMedCrossRefGoogle Scholar
  31. Nduulu LM, Mesfin A, Muehlbauer GJ, Smith KP (2007) Analysis of the chromosome 2 (2H) region of barley associated with the correlated traits Fusarium head blight resistance and heading date. Theor Appl Genet 115:561–570PubMedCrossRefGoogle Scholar
  32. Ordonez SA, Silva J, Oard JH (2010) Association mapping of grain quality and flowering in elite japonica rice germplasm. J Cereal Sci 51:337–343CrossRefGoogle Scholar
  33. Pressoir G, Brown PJ, Zhu W, Upadyayula N, Rocheford T, Buckler ES, Kresovich S (2009) Natural variation in maize architecture is mediated by allelic differences at the PINOID co-ortholog barren inflorescence2. Plant J 58:618–628PubMedCrossRefGoogle Scholar
  34. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38:904–909PubMedCrossRefGoogle Scholar
  35. Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959PubMedGoogle Scholar
  36. Ramsay L, Comadran J, Druka A, Marshall DF, Thomas WTB, Macaulay M, MacKenzie K, Simpson C, Fuller J, Bonar N, Hayes PM, Lundqvist U, Franckowiak JD, Close TJ, Muehlbauer GJ, Waugh R (2011) INTERMEDIUM-C, a modifier of lateral spikelet fertility in barley, is an ortholog of the maize domestication gene TEOSINTE BRANCHED 1. Nat Genet 43:169–172PubMedCrossRefGoogle Scholar
  37. Rostoks N, Mudie S, Cardle L, Russell J, Ramsay L, Booth A, Svensson JT, Wanamaker SI, Walia H, Rodriguez EM (2005) Genome-wide SNP discovery and linkage analysis in barley based on genes responsive to abiotic stress. Mol Genet Genomics 274:515–527PubMedCrossRefGoogle Scholar
  38. Rostoks N, Ramsay L, MacKenzie K, Cardle L, Bhat PR, Roose ML, Svensson JT, Stein N, Varshney RK, Marshall DF (2006) Recent history of artificial outcrossing facilitates whole-genome association mapping in elite inbred crop varieties. Proc Natl Acad Sci USA 103:18656–18661PubMedCrossRefGoogle Scholar
  39. Roy JK, Smith KP, Muehlbauer GJ, Chao S, Close TJ, Steffenson BJ (2010) Association mapping of spot blotch resistance in wild barley. Mol Breed 26:243–256PubMedCrossRefGoogle Scholar
  40. Slate J, Pemberton JM (2007) Admixture and patterns of linkage disequilibrium in a free‐living vertebrate population. J Evol Biol 20:1415–1427PubMedCrossRefGoogle Scholar
  41. Slotta TA, Brady L, Chao S (2008) High throughput tissue preparation for large‐scale genotyping experiments. Mol Ecol Resour 8:83–87PubMedCrossRefGoogle Scholar
  42. Smith A, Cullis B, Thompson R (2001) Analyzing variety by environment data using multiplicative mixed models and adjustments for spatial field trend. Biometrics 57:1138–1147PubMedCrossRefGoogle Scholar
  43. Smith AB, Cullis BR, Thompson R (2005) The analysis of crop cultivar breeding and evaluation trials: an overview of current mixed model approaches. J Agric Sci 143:449–462CrossRefGoogle Scholar
  44. Spaner D, Shugar LP, Choo TM, Falak I, Briggs KG, Legge WG, Falk DE, Ullrich SE, Tinker NA, Steffenson BJ, Mather DE (1998) Mapping of disease resistance loci in barley on the basis of visual assessment of naturally occurring symptoms. Crop Sci 38:843–850CrossRefGoogle Scholar
  45. Spilke J, Piepho HP, Hu X (2005) Analysis of unbalanced data by mixed linear models using the MIXED procedure of the SAS system. J Agron Crop Sci 191:47–54CrossRefGoogle Scholar
  46. Stich B, Möhring J, Piepho HP, Heckenberger M, Buckler ES, Melchinger AE (2008) Comparison of mixed-model approaches for association mapping. Genetics 178:1745–1754PubMedCrossRefGoogle Scholar
  47. Thornsberry JM, Goodman MM, Doebley J, Kresovich S, Nielsen D, Buckler ES (2001) Dwarf8 polymorphisms associate with variation in flowering time. Nat Genet 28:286–289PubMedCrossRefGoogle Scholar
  48. Vales MI, Schön CC, Capettini F, Chen XM, Corey AE, Mather DE, Mundt CC, Richardson KL, Sandoval-Islas JS, Utz HF, Hayes PM (2005) Effect of population size on the estimation of QTL: a test using resistance to barley stripe rust. Theor Appl Genet 111:1260–1270PubMedCrossRefGoogle Scholar
  49. von Zitzewitz J, Condon F, Corey A, Cuesta-Marcos A, Filichkina T, Haggard K, Fisk SP, Smith KP, Muehlbauer GJ, Karsai I, Hayes PM (2011) The genetics of winterhardiness in barley: perspectives from genome-wide association mapping. The Plant Genome 4:76–91CrossRefGoogle Scholar
  50. Wang J, McClean PE, Lee R, Goos RJ, Helms T (2008) Association mapping of iron deficiency chlorosis loci in soybean (Glycine max L. Merr.) advanced breeding lines. Theor Appl Genet 116:777–787PubMedCrossRefGoogle Scholar
  51. Waugh R, Jannink JL, Muehlbauer GJ, Ramsay L (2009) The emergence of whole genome association scans in barley. Curr Opin Plant Biol 12:218–222PubMedCrossRefGoogle Scholar
  52. Wilson LM, Whitt SR, Ibanez AM, Rocheford TR, Goodman MM, ES BucklerIV (2004) Dissection of maize kernel composition and starch production by candidate gene association. Plant Cell 16:2719–2733PubMedCrossRefGoogle Scholar
  53. Yan L, Fu D, Li C, Blechl A, Tranquilli G, Bonafede M, Sanchez A, Valarik M, Yasuda S, Dubcovsky J (2006) The wheat and barley vernalization gene VRN3 is an orthologue of FT. Proc Natl Acad Sci USA 103:19581–19586PubMedCrossRefGoogle Scholar
  54. Yu J, Pressoir G, Briggs WH, Bi IV, Yamasaki M, Doebley JF, McMullen MD, Gaut BS, Nielsen DM, Holland JB (2006) A unified mixed-model method for association mapping that accounts for multiple levels of relatedness. Nat Genet 38:203–208PubMedCrossRefGoogle Scholar
  55. Zhang Z, Ersoz E, Lai CQ, Todhunter RJ, Tiwari HK, Gore MA, Bradbury PJ, Yu J, Arnett DK, Ordovas JM, Buckler ES (2010) Mixed linear model approach adapted for genome-wide association studies. Nat Genet 42:355–360PubMedCrossRefGoogle Scholar
  56. Zhao K, Aranzana MJ, Kim S, Lister C, Shindo C, Tang C, Toomajian C, Zheng H, Dean C, Marjoram P (2007) An Arabidopsis example of association mapping in structured samples. PLoS Genet 3:e4PubMedCrossRefGoogle Scholar
  57. Zhu C, Gore M, Buckler ES, Yu J (2008) Status and prospects of association mapping in plants. Plant Genome 1:5–20CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Hongyun Wang
    • 1
  • Kevin P. Smith
    • 1
  • Emily Combs
    • 1
  • Tom Blake
    • 2
  • Richard D. Horsley
    • 3
  • Gary J. Muehlbauer
    • 1
    Email author
  1. 1.Department of Agronomy and Plant GeneticsUniversity of MinnesotaSt. PaulUSA
  2. 2.Department of Plant Sciences and Plant PathologyMontana State UniversityBozemanUSA
  3. 3.Department of Plant SciencesNorth Dakota State UniversityFargoUSA

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