A Multiparent Advanced Generation Inter-Cross to Fine-Map Quantitative Traits in Arabidopsis thaliana

Identifying natural allelic variation that underlies quantitative trait variation remains a fundamental problem in genetics. Most studies have employed either simple synthetic populations with restricted allelic variation or performed association mapping on a sample of naturally occurring haplotypes. Both of these approaches have some limitations, therefore alternative resources for the genetic dissection of complex traits continue to be sought. Here we describe one such alternative, the Multiparent Advanced Generation Inter-Cross (MAGIC). This approach is expected to improve the precision with which QTL can be mapped, improving the outlook for QTL cloning. Here, we present the first panel of MAGIC lines developed: a set of 527 recombinant inbred lines (RILs) descended from a heterogeneous stock of 19 intermated accessions of the plant Arabidopsis thaliana. These lines and the 19 founders were genotyped with 1,260 single nucleotide polymorphisms and phenotyped for development-related traits. Analytical methods were developed to fine-map quantitative trait loci (QTL) in the MAGIC lines by reconstructing the genome of each line as a mosaic of the founders. We show by simulation that QTL explaining 10% of the phenotypic variance will be detected in most situations with an average mapping error of about 300 kb, and that if the number of lines were doubled the mapping error would be under 200 kb. We also show how the power to detect a QTL and the mapping accuracy vary, depending on QTL location. We demonstrate the utility of this new mapping population by mapping several known QTL with high precision and by finding novel QTL for germination data and bolting time. Our results provide strong support for similar ongoing efforts to produce MAGIC lines in other organisms.

[1]  William Valdar,et al.  Mapping in Structured Populations by Resample Model Averaging , 2009, Genetics.

[2]  Detlef Weigel,et al.  QTL Mapping in New Arabidopsis thaliana Advanced Intercross-Recombinant Inbred Lines , 2009, PloS one.

[3]  Detlef Weigel,et al.  Next-generation genetics in plants , 2008, Nature.

[4]  Richard M. Clark,et al.  Sequencing of natural strains of Arabidopsis thaliana with short reads. , 2008, Genome research.

[5]  Elissa J. Chesler,et al.  The Collaborative Cross at Oak Ridge National Laboratory: developing a powerful resource for systems genetics , 2008, Mammalian Genome.

[6]  Alan M. Jones,et al.  The Impact of Arabidopsis on Human Health: Diversifying Our Portfolio , 2008, Cell.

[7]  R. Mott,et al.  The Collaborative Cross, developing a resource for mammalian systems genetics: A status report of the Wellcome Trust cohort , 2008, Mammalian Genome.

[8]  O. Loudet,et al.  Quantitative Trait Loci Mapping in Five New Large Recombinant Inbred Line Populations of Arabidopsis thaliana Genotyped With Consensus Single-Nucleotide Polymorphism Markers , 2008, Genetics.

[9]  W. Powell,et al.  From mutations to MAGIC: resources for gene discovery, validation and delivery in crop plants. , 2008, Current opinion in plant biology.

[10]  D. Heckerman,et al.  Efficient Control of Population Structure in Model Organism Association Mapping , 2008, Genetics.

[11]  M. Koornneef,et al.  A mixed model QTL analysis for a complex cross population consisting of a half diallel of two-way hybrids in Arabidopsis thaliana: analysis of simulated data , 2008, Euphytica.

[12]  M. Piotrowski,et al.  Maize nitrilases have a dual role in auxin homeostasis and beta-cyanoalanine hydrolysis. , 2007, Journal of experimental botany.

[13]  J. Cheverud,et al.  Antagonistic pleiotropic effects reduce the potential adaptive value of the FRIGIDA locus , 2007, Proceedings of the National Academy of Sciences.

[14]  Detlef Weigel,et al.  Recombination and linkage disequilibrium in Arabidopsis thaliana , 2007, Nature Genetics.

[15]  Richard M. Clark,et al.  Common Sequence Polymorphisms Shaping Genetic Diversity in Arabidopsis thaliana , 2007, Science.

[16]  Martin S. Taylor,et al.  Management, presentation and interpretation of genome scans using GSCANDB , 2007, Bioinform..

[17]  A. Long,et al.  Joint Estimates of Quantitative Trait Locus Effect and Frequency Using Synthetic Recombinant Populations of Drosophila melanogaster , 2007, Genetics.

[18]  B. Payseur,et al.  Prospects for Association Mapping in Classical Inbred Mouse Strains , 2007, Genetics.

[19]  Keyan Zhao,et al.  An Arabidopsis Example of Association Mapping in Structured Samples , 2006, PLoS genetics.

[20]  Hongwei Guo,et al.  ETHYLENE-INSENSITIVE5 encodes a 5′→3′ exoribonuclease required for regulation of the EIN3-targeting F-box proteins EBF1/2 , 2006, Proceedings of the National Academy of Sciences.

[21]  Martin S. Taylor,et al.  Genome-wide genetic association of complex traits in heterogeneous stock mice , 2006, Nature Genetics.

[22]  A. Fernie,et al.  Natural genetic variation for improving crop quality. , 2006, Current opinion in plant biology.

[23]  M. Koornneef,et al.  New Arabidopsis Recombinant Inbred Line Populations Genotyped Using SNPWave and Their Use for Mapping Flowering-Time Quantitative Trait Loci , 2006, Genetics.

[24]  William Valdar,et al.  Simulating the Collaborative Cross: Power of Quantitative Trait Loci Detection and Mapping Resolution in Large Sets of Recombinant Inbred Strains of Mice , 2006, Genetics.

[25]  R. Mott,et al.  Using Progenitor Strain Information to Identify Quantitative Trait Nucleotides in Outbred Mice , 2005, Genetics.

[26]  M. Nordborg,et al.  Role of FRIGIDA and FLOWERING LOCUS C in Determining Variation in Flowering Time of Arabidopsis1[w] , 2005, Plant Physiology.

[27]  Jorge J Casal,et al.  Mapping Quantitative Trait Loci in Multiple Populations of Arabidopsis thaliana Identifies Natural Allelic Variation for Trichome Density , 2005, Genetics.

[28]  M. Koornneef,et al.  From phenotypic to molecular polymorphisms involved in naturally occurring variation of plant development. , 2005, The International journal of developmental biology.

[29]  Nengjun Yi,et al.  The Collaborative Cross, a community resource for the genetic analysis of complex traits , 2004, Nature Genetics.

[30]  S. Tabata,et al.  Exploitation of colinear relationships between the genomes of Lotus japonicus, Pisum sativum and Arabidopsis thaliana, for positional cloning of a legume symbiosis gene , 2004, Theoretical and Applied Genetics.

[31]  S. Tanksley,et al.  QTL analysis of trichome-mediated insect resistance in potato , 1994, Theoretical and Applied Genetics.

[32]  M. Schmid,et al.  Genome-Wide Insertional Mutagenesis of Arabidopsis thaliana , 2003, Science.

[33]  M. Koornneef,et al.  Analysis of natural allelic variation at seed dormancy loci of Arabidopsis thaliana. , 2003, Genetics.

[34]  K. Halliday,et al.  Changes in Photoperiod or Temperature Alter the Functional Relationships between Phytochromes and Reveal Roles for phyD and phyE1 , 2003, Plant Physiology.

[35]  H. Kamada,et al.  Ethylene advances the transition from vegetative growth to flowering in Arabidopsis thaliana. , 2003, Journal of plant physiology.

[36]  Shoshi Kikuchi,et al.  Comprehensive analysis of NAC family genes in Oryza sativa and Arabidopsis thaliana. , 2003, DNA research : an international journal for rapid publication of reports on genes and genomes.

[37]  B. Schaal,et al.  Genetic variation for disease resistance and tolerance among Arabidopsis thaliana accessions , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[38]  R. Last,et al.  Arabidopsis Map-Based Cloning in the Post-Genome Era , 2002, Plant Physiology.

[39]  Massimo Pigliucci,et al.  Touchy and Bushy: Phenotypic Plasticity and Integration in Response to Wind Stimulation in Arabidopsis thaliana , 2002, International Journal of Plant Sciences.

[40]  W. J. Kent,et al.  BLAT--the BLAST-like alignment tool. , 2002, Genome research.

[41]  T. Mackay,et al.  Quantitative trait loci for inflorescence development in Arabidopsis thaliana. , 2002, Genetics.

[42]  O. Loudet,et al.  Bay-0 × Shahdara recombinant inbred line population: a powerful tool for the genetic dissection of complex traits in Arabidopsis , 2002, Theoretical and Applied Genetics.

[43]  Shizhong Xu QTL analysis in plants. , 2002, Methods in molecular biology.

[44]  S. Somerville,et al.  Polygenic powdery mildew disease resistance in Arabidopsis thaliana: quantitative trait analysis of the accession Warschau‐1 , 2001 .

[45]  G. Churchill,et al.  A statistical framework for quantitative trait mapping. , 2001, Genetics.

[46]  S. Somerville,et al.  Quantitative trait loci analysis of powdery mildew disease resistance in the Arabidopsis thaliana accession kashmir-1. , 2001, Genetics.

[47]  K. Broman,et al.  Review of statistical methods for QTL mapping in experimental crosses. , 2001, Lab animal.

[48]  A. C. Collins,et al.  A method for fine mapping quantitative trait loci in outbred animal stocks. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[49]  R. Amasino,et al.  Molecular analysis of FRIGIDA, a major determinant of natural variation in Arabidopsis flowering time. , 2000, Science.

[50]  W. Lukowitz,et al.  Positional cloning in Arabidopsis. Why it feels good to have a genome initiative working for you. , 2000, Plant physiology.

[51]  A. Peeters,et al.  The genetics of seed dormancy in Arabidopsis thaliana. , 2000 .

[52]  M Koornneef,et al.  Naturally occurring variation in Arabidopsis: an underexploited resource for plant genetics. , 2000, Trends in plant science.

[53]  M. Kearsey,et al.  More QTL for flowering time revealed by substitution lines in Brassica oleracea , 1999, Heredity.

[54]  David W. Fulker,et al.  High-resolution mapping of quantitative trait loci in outbred mice , 1999, Nature Genetics.

[55]  R. S. Kobayashi,et al.  Identification of molecular markers associated with leptine production in a population of Solanum chacoense Bitter , 1999, Theoretical and Applied Genetics.

[56]  G. C. Yencho,et al.  QTL mapping of foliar glycoalkaloid aglycones in Solanum tuberosum×S. berthaultii potato progenies: quantitative variation and plant secondary metabolism , 1998, Theoretical and Applied Genetics.

[57]  M. Kearsey,et al.  QTL analysis in plants; where are we now? , 1998, Heredity.

[58]  Z. Zeng Precision mapping of quantitative trait loci. , 1994, Genetics.

[59]  C. Haley,et al.  A simple regression method for mapping quantitative trait loci in line crosses using flanking markers , 1992, Heredity.

[60]  E. Lander,et al.  Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. , 1989, Genetics.