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 they 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 new associations and evidence for allelic heterogeneity. We also show 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 data sets (n > 10,000) practicable.
It is well known that abscisic acid (ABA) promotes reactive oxygen species (ROS) production through plasma membrane–associated NADPH oxidases during ABA signaling. However, whether ROS from organelles can act as second messengers in ABA signaling is largely unknown. Here, we identified an ABA overly sensitive mutant, abo6, in a genetic screen for ABA-mediated inhibition of primary root growth. ABO6 encodes a DEXH box RNA helicase that is involved in regulating the splicing of several genes of complex I in mitochondria. The abo6 mutant accumulated more ROS in mitochondria, as established using a mitochondrial superoxide indicator, circularly permuted yellow fluorescent protein. Two dominant-negative mutations in ABA insensitive1 (abi1-1) and abi2-1 greatly reduced ROS production in mitochondria. The ABA sensitivity of abo6 can also be compromised by the atrbohF mutation. ABA-mediated inhibition of seed germination and primary root growth in abo6 was released by the addition of reduced GSH and exogenous auxin to the medium. Expression of auxin-responsive markers ProDR5:GUS (for synthetic auxin response element D1-4 with site-directed mutants in the 5′-end from soybean):β-glucuronidase) and Indole-3-acetic acid inducible2:GUS was greatly reduced by the abo6 mutation. Hence, our results provide molecular evidence for the interplay between ABA and auxin through the production of ROS from mitochondria. This interplay regulates primary root growth and seed germination in Arabidopsis thaliana.