Recent history of artificial outcrossing facilitates whole-genome association mapping in elite inbred crop varieties

Genomewide association studies depend on the extent of linkage disequilibrium (LD), the number and distribution of markers, and the underlying structure in populations under study. Outbreeding species generally exhibit limited LD, and consequently, a very large number of markers are required for effective whole-genome association genetic scans. In contrast, several of the world's major food crops are self-fertilizing inbreeding species with narrow genetic bases and theoretically extensive LD. Together these are predicted to result in a combination of low resolution and a high frequency of spurious associations in LD-based studies. However, inbred elite plant varieties represent a unique human-induced pseudooutbreeding population that has been subjected to strong selection for advantageous alleles. By assaying 1,524 genomewide SNPs we demonstrate that, after accounting for population substructure, the level of LD exhibited in elite northwest European barley, a typical inbred cereal crop, can be effectively exploited to map traits by using whole-genome association scans with several hundred to thousands of biallelic SNPs.

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

[2]  Sarah A Tishkoff,et al.  Patterns of human genetic diversity: implications for human evolutionary history and disease. , 2003, Annual review of genomics and human genetics.

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

[4]  J. Witte,et al.  Genetic dissection of complex traits. , 1994, Nature genetics.

[5]  R. Waugh,et al.  Integration of microsatellite markers into the translocation-based physical RFLP map of barley chromosome 3H , 2002, Theoretical and Applied Genetics.

[6]  Analysis of microliter volumes of dye-labeled nucleic acids. , 2002, BioTechniques.

[7]  P. Langridge,et al.  Comparative Sequence Analysis of the Region Harboring the Hardness Locus in Barley and Its Colinear Region in Rice1 , 2004, Plant Physiology.

[8]  E S Buckler,et al.  Structure of linkage disequilibrium and phenotypic associations in the maize genome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Harlan,et al.  The Living Fields: Our Agricultural Heritage. , 1995 .

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

[11]  E. Stockinger,et al.  Mapping of barley homologs to genes that regulate low temperature tolerance in Arabidopsis , 2006, Theoretical and Applied Genetics.

[12]  J. Harlan,et al.  The Living Fields: Our Agricultural Heritage. , 1995 .

[13]  Xavier Messeguer,et al.  DnaSP, DNA polymorphism analyses by the coalescent and other methods , 2003, Bioinform..

[14]  Han,et al.  Sequence analysis of a rice BAC covering the syntenous barley Rpg1 region , 1999, Genome.

[15]  S. Wanamaker,et al.  Genome-wide SNP discovery and linkage analysis in barley based on genes responsive to abiotic stress , 2005, Molecular Genetics and Genomics.

[16]  L. Cooper,et al.  Positional relationships between photoperiod response QTL and photoreceptor and vernalization genes in barley , 2006, Theoretical and Applied Genetics.

[17]  P. Oefner,et al.  The extent of linkage disequilibrium in Arabidopsis thaliana , 2002, Nature Genetics.

[18]  D. Kudrna,et al.  Molecular mapping of the Oregon Wolfe Barleys: a phenotypically polymorphic doubled-haploid population , 2001, Theoretical and Applied Genetics.

[19]  B. Gaut,et al.  Genetic diversity and selection in the maize starch pathway , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[20]  P. Smouse,et al.  genalex 6: genetic analysis in Excel. Population genetic software for teaching and research , 2006 .

[21]  D Bentley,et al.  Highly parallel SNP genotyping. , 2003, Cold Spring Harbor symposia on quantitative biology.

[22]  S. Tanksley,et al.  Seed banks and molecular maps: unlocking genetic potential from the wild. , 1997, Science.

[23]  L. Ramsay,et al.  Comparison of RAMP and SSR markers for the study of wild barley genetic diversity. , 2004, Hereditas.

[24]  M. Stephens,et al.  Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. , 2003, Genetics.

[25]  Simon Tavaré,et al.  Linkage disequilibrium: what history has to tell us. , 2002, Trends in genetics : TIG.

[26]  P. Schulze-Lefert,et al.  A barley cultivation-associated polymorphism conveys resistance to powdery mildew , 2004, Nature.

[27]  E. Stockinger,et al.  Structural, Functional, and Phylogenetic Characterization of a Large CBF Gene Family in Barley , 2005, Plant Molecular Biology.

[28]  L. Kruglyak,et al.  Patterns of linkage disequilibrium in the human genome , 2002, Nature Reviews Genetics.

[29]  Allan Booth,et al.  A comparison of sequence-based polymorphism and haplotype content in transcribed and anonymous regions of the barley genome. , 2004, Genome.

[30]  A. Meister,et al.  Cytologically integrated physical restriction fragment length polymorphism maps for the barley genome based on translocation breakpoints. , 2000, Genetics.

[31]  P. Hayes,et al.  Molecular and Structural Characterization of Barley Vernalization Genes , 2005, Plant Molecular Biology.

[32]  P. Langridge,et al.  Extreme Population-Dependent Linkage Disequilibrium Detected in an Inbreeding Plant Species, Hordeum vulgare , 2006, Genetics.

[33]  D. Kudrna,et al.  A molecular, isozyme and morphological map of the barley (Hordeum vulgare) genome , 1993, Theoretical and Applied Genetics.

[34]  K. Bussell.  Signalling: Friendly rivalry , 2005, Nature Reviews Molecular Cell Biology.

[35]  D. Botstein,et al.  Construction of a genetic linkage map in man using restriction fragment length polymorphisms. , 1980, American journal of human genetics.

[36]  M. Daly,et al.  Genome-wide association studies for common diseases and complex traits , 2005, Nature Reviews Genetics.

[37]  P. Hayes,et al.  Two loci on chromosome 5H determine low-temperature tolerance in a ‘Nure’ (winter) × ‘Tremois’ (spring) barley map , 2004, Theoretical and Applied Genetics.

[38]  Jeffrey C. Hall,et al.  Advances in Genetics , 1947 .

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

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