Genome-wide association mapping to candidate polymorphism resolution in the unsequenced barley genome.

Although commonplace in human disease genetics, genome-wide association (GWA) studies have only relatively recently been applied to plants. Using 32 phenotypes in the inbreeding crop barley, we report GWA mapping of 15 morphological traits across ∼500 cultivars genotyped with 1,536 SNPs. In contrast to the majority of human GWA studies, we observe high levels of linkage disequilibrium within and between chromosomes. Despite this, GWA analysis readily detected common alleles of high penetrance. To investigate the potential of combining GWA mapping with comparative analysis to resolve traits to candidate polymorphism level in unsequenced genomes, we fine-mapped a selected phenotype (anthocyanin pigmentation) within a 140-kb interval containing three genes. Of these, resequencing the putative anthocyanin pathway gene HvbHLH1 identified a deletion resulting in a premature stop codon upstream of the basic helix-loop-helix domain, which was diagnostic for lack of anthocyanin in our association and biparental mapping populations. The methodology described here is transferable to species with limited genomic resources, providing a paradigm for reducing the threshold of map-based cloning in unsequenced crops.

Divergence pattern of duplicate genes in protein-protein interactions follows the power law.

The impact of the biological network structures on the divergence between the two copies of one duplicate gene pair involved in the networks has not been documented on a genome scale. Having analyzed the most recently updated Database of Interacting Proteins (DIP) by incorporating the information for duplicate genes of the same age in yeast, we find that there was a highly significantly positive correlation between the level of connectivity of ancient genes and the number of shared partners of their duplicates in the protein-protein interaction networks. This suggests that duplicate genes with a low ancestral connectivity tend to provide raw materials for functional novelty, whereas those duplicate genes with a high ancestral connectivity tend to create functional redundancy for a genome during the same evolutionary period. Moreover, the difference in the number of partners between two copies of a duplicate pair was found to follow a power-law distribution. This suggests that loss and gain of interacting partners for most duplicate genes with a lower level of ancestral connectivity is largely symmetrical, whereas the "hub duplicate genes" with a higher level of ancient connectivity display an asymmetrical divergence pattern in protein-protein interactions. Thus, it is clear that the protein-protein interaction network structures affect the divergence pattern of duplicate genes. Our findings also provide insights into the origin and development of biological networks.

STAIRS: a new genetic resource for functional genomic studies of Arabidopsis.

Many biologically and economically important traits in plants and animals are quantitative/multifactorial, being controlled by several quantitative trait loci (QTL). QTL are difficult to locate accurately by conventional methods using molecular markers in segregating populations, particularly for traits of low heritability or for QTL with small effects. In order to resolve this, large (often unrealistically large) populations are required. In this paper we present an alternative approach using a specially developed resource of lines that facilitate QTL location first to a particular chromosome, then to successively smaller regions within a chromosome (< or = 0.5 cM) by means of simple comparisons among a few lines. This resource consists of "Stepped Aligned Inbred Recombinant Strains" (STAIRS) plus single whole Chromosome Substitution Strains (CSSs). We explain the analytical power of STAIRS and illustrate their construction and use with Arabidopsis thaliana, although the principles could be applied to many organisms. We were able to locate flowering QTL at the top of chromosome 3 known to contain several potential candidate genes.