Search

Population structure causes genome-wide linkage disequilibrium between unlinked loci, leading to statistical confounding in genome-wide association studies. Mixed models have been shown to handle the confounding effects of a diffuse background of large numbers of loci of small effect well, but do not always account for loci of larger effect. Here we propose a multi-locus mixed model as a general method for mapping complex traits in structured populations. Simulations suggest that our method outperforms existing methods, in terms of power as well as false discovery rate. We apply our method to human and Arabidopsis thaliana data, identifying novel associations in known candidates as well as evidence for allelic heterogeneity. We also demonstrate how a priori knowledge from an A. thaliana linkage mapping study can be integrated into our method using a Bayesian approach. Our implementation is computationally efficient, making the analysis of large datasets (n > 10000) practicable.

Arabidopsis thaliana is an important model organism for understanding the genetics and molecular biology of plants. Its highly selfing nature, small size, short generation time, small genome size, and wide geographic distribution make it an ideal model organism for understanding natural variation. Genome-wide association studies (GWAS) have proven a useful technique for identifying genetic loci responsible for natural variation in A. thaliana. Previously genotyped accessions (natural inbred lines) can be grown in replicate under different conditions and phenotyped for different traits. These important features greatly simplify association mapping of traits and allow for systematic dissection of the genetics of natural variation by the entire A. thaliana community. To facilitate this, we present GWAPP, an interactive Web-based application for conducting GWAS in A. thaliana. Using an efficient implementation of a linear mixed model, traits measured for a subset of 1386 publicly available ecotypes can be uploaded and mapped with a mixed model and other methods in just a couple of minutes. GWAPP features an extensive, interactive, and user-friendly interface that includes interactive Manhattan plots and linkage disequilibrium plots. It also facilitates exploratory data analysis by implementing features such as the inclusion of candidate polymorphisms in the model as cofactors.

absent

International audience; Marker informed breeding could be a favorable opportunity to accelerate cultivar selection in poplar. Linking genotype to phenotypic variation of important economical and adaptive traits is the prerequisite. The two strategies chosen are QTL detection in mapping pedigrees and association studies in natural populations. An intra-specific mapping pedigree Populus nigra x P. nigra of 300 individuals segregating for leaf rust resistance is available. Another large progeny of 1400 individuals derived from a cross P. deltoides x P. trichocarpa for which two major factors and QTL of rust resistance segregated is already available. QTL for phenology and water use efficiency were also mapped. Large scale phenotyping of wood properties is underway. An association mapping population of 1100 P. nigra individuals coming from France, Germany, Netherlands and Spain was evaluated for rust resistance in both controlled and field conditions. Even if most of the genetic variation for rust resistance could be observed at the genotype level, significant differentiation between natural populations was detected. Taking advantages of genomics development in poplar including structural and functional genomics, positional, functional and expressional candidate genes were identified for rust resistance, phenology and wood properties. It became clear that SNP in those genes could be ideal combined to HTP genotyping technologies to identify causative polymorphism for phenotypic variation. We developed collections of SNP useful for both genetic and association mapping. With the help of the genome sequence, unique primer pairs were automatically designed and tested for their uniqueness before PCR amplification and HTP Sanger re-sequencing. Based on the analysis of 850 gene fragments, an average of 1SNP/90bp were found in the three Populus species studied. SNP appeared fixed in each species after comparison of SNP position between the three species. Analysis of linkage disequilibrium in P. nigra showed a rapid decline of LD with physical distance