Bayesian association mapping of multiple quantitative trait loci and its application to the analysis of genetic variation among Oryza sativa L. germplasms

One way to use a crop germplasm collection directly to map QTLs without using line-crossing experiments is the whole genome association mapping. A major problem with association mapping is the presence of population structure, which can lead to both false positives and failure to detect genuine associations (i.e., false negatives). Particularly in highly selfing species such as Asian cultivated rice, high levels of population structure are expected and therefore the efficiency of association mapping remains almost unknown. Here, we propose an approach that combines a Bayesian method for mapping multiple QTLs with a regression method that directly incorporates estimates of population structure. That is, the effects due to both multiple QTLs and population structure were included in our statistical model. We evaluated the efficiency of our approach in simulated- and real-trait analyses of a rice germplasm collection. Simulation analyses based on real marker data showed that our model could suppress both false-positive and false-negative rates and the error of estimation of genetic effects over single QTL models, indicating that our model has statistically desirable attributes over single QTL models. As real traits, we analyzed the size and shape of milled rice grains and found significant markers that may be linked to QTLs reported previously. Association mapping should have good prospects in highly selfing species such as rice if proper methods are adopted. Our approach will be useful for the whole genome association mapping of various selfing crop species.

[1]  Edward S. Buckler,et al.  Dwarf8 polymorphisms associate with variation in flowering time , 2001, Nature Genetics.

[2]  S. Lin,et al.  A high-density rice genetic linkage map with 2275 markers using a single F2 population. , 1998, Genetics.

[3]  Nengjun Yi,et al.  Stochastic search variable selection for identifying multiple quantitative trait loci. , 2003, Genetics.

[4]  M. Sillanpää,et al.  Bayesian mapping of multiple quantitative trait loci from incomplete outbred offspring data. , 1999, Genetics.

[5]  L. Tsui,et al.  Erratum: Identification of the Cystic Fibrosis Gene: Genetic Analysis , 1989, Science.

[6]  Susan McCouch,et al.  RFLP mapping of isozymes, RAPD and QTLs for grain shape, brown planthopper resistance in a doubled haploid rice population , 2004, Molecular Breeding.

[7]  J. Tohme,et al.  QTL mapping of grain quality traits from the interspecific cross Oryza sativa × O. glaberrima , 2004, Theoretical and Applied Genetics.

[8]  S. Mccouch,et al.  Identification of candidate markers associated with agronomic traits in rice using discriminant analysis , 2005, Theoretical and Applied Genetics.

[9]  M. Sillanpää,et al.  Bayesian mapping of multiple quantitative trait loci from incomplete inbred line cross data. , 1998, Genetics.

[10]  R. Bernardo,et al.  In silico mapping of quantitative trait loci in maize , 2004, Theoretical and Applied Genetics.

[11]  S. Heath Markov chain Monte Carlo segregation and linkage analysis for oligogenic models. , 1997, American journal of human genetics.

[12]  Jinhua Xiao,et al.  QTL detection for rice grain quality traits using an interspecific backcross population derived from cultivated Asian (O. sativa L.) and African (O. glaberrima S.) rice. , 2004, Genome.

[13]  H. Zhai,et al.  Stability of QTLs for rice grain dimension and endosperm chalkiness characteristics across eight environments , 2005, Theoretical and Applied Genetics.

[14]  D. Mackill,et al.  Quantitative trait locus analysis for rice panicle and grain characteristics , 1998, Theoretical and Applied Genetics.

[15]  E. Lander,et al.  Genetic dissection of complex traits science , 1994 .

[16]  P. Donnelly,et al.  Association mapping in structured populations. , 2000, American journal of human genetics.

[17]  Mikko J Sillanpää,et al.  Bayesian Association-Based Fine Mapping in Small Chromosomal Segments , 2005, Genetics.

[18]  E. George,et al.  Journal of the American Statistical Association is currently published by American Statistical Association. , 2007 .

[19]  A. Brown,et al.  Core collections: a practical approach to genetic resources management , 1989 .

[20]  R. Williams,et al.  Gm3;5,13,14 and type 2 diabetes mellitus: an association in American Indians with genetic admixture. , 1988, American journal of human genetics.

[21]  Bayesian mapping of QTL in outbred F2 families allowing inference about whether F0 grandparents are homozygous or heterozygous at QTL , 2005, Heredity.

[22]  M A Newton,et al.  A bayesian approach to detect quantitative trait loci using Markov chain Monte Carlo. , 1996, Genetics.

[23]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[24]  Bin Han,et al.  GS3, a major QTL for grain length and weight and minor QTL for grain width and thickness in rice, encodes a putative transmembrane protein , 2006, Theoretical and Applied Genetics.

[25]  M. Sillanpää,et al.  Bayesian oligogenic analysis of quantitative and qualitative traits in general pedigrees , 2001, Genetic epidemiology.

[26]  L. Tsui,et al.  Identification of the cystic fibrosis gene: genetic analysis. , 1989, Science.

[27]  Mikko J Sillanpää,et al.  Bayesian analysis of multilocus association in quantitative and qualitative traits , 2003, Genetic epidemiology.

[28]  M. McMullen,et al.  A unified mixed-model method for association mapping that accounts for multiple levels of relatedness , 2006, Nature Genetics.

[29]  Kermit Ritland,et al.  Estimators for pairwise relatedness and individual inbreeding coefficients , 1996 .

[30]  Shizhong Xu,et al.  Mapping Quantitative Trait Loci Using Naturally Occurring Genetic Variance Among Commercial Inbred Lines of Maize (Zea mays L.) , 2005, Genetics.

[31]  J. L. Wang,et al.  QTL analysis for rice grain length and fine mapping of an identified QTL with stable and major effects , 2006, Theoretical and Applied Genetics.

[32]  Nengjun Yi,et al.  A Unified Markov Chain Monte Carlo Framework for Mapping Multiple Quantitative Trait Loci , 2004, Genetics.

[33]  M. Sorrells,et al.  Association Mapping of Kernel Size and Milling Quality in Wheat (Triticum aestivum L.) Cultivars , 2006, Genetics.

[34]  I. Hoeschele,et al.  Mapping-linked quantitative trait loci using Bayesian analysis and Markov chain Monte Carlo algorithms. , 1997, Genetics.

[35]  E. Buckler,et al.  Structure of linkage disequilibrium in plants. , 2003, Annual review of plant biology.

[36]  M. Kawase,et al.  Development of an RFLP-based Rice Diversity Research Set of Germplasm , 2005 .

[37]  A. M. Saunders,et al.  Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease , 1994, Nature Genetics.

[38]  S. Lin,et al.  A 300 kilobase interval genetic map of rice including 883 expressed sequences , 1994, Nature Genetics.

[39]  P. Donnelly,et al.  Inference of population structure using multilocus genotype data. , 2000, Genetics.

[40]  F. V. van Eeuwijk,et al.  Linkage Disequilibrium Mapping of Yield and Yield Stability in Modern Spring Barley Cultivars , 2004, Genetics.