Genome-wide mapping with biallelic markers in Arabidopsis thaliana

Single-nucleotide polymorphisms, as well as small insertions and deletions (here referred to collectively as simple nucleotide polymorphisms, or SNPs) , comprise the largest set of sequence variants in most organisms(1,2). Pos itional cloning based on SNPs may accelerate the identification of human di sease traits and a range of biologically informative mutations(3-6). The re cent application of high-density oligonucleotide arrays to allele identific ation has made it feasible to genotype thousands of biallelic SNPs in a sin gle experiment(3,7). It has yet to be established, however, whether SNP det ection using oligonucleotide arrays can be used to accelerate the mapping o f traits in diploid genomes. The cruciferous weed Arabidopsis thaliana is a n attractive model system for the construction and use of biallelic SNP map s. Although important biological processes ranging from fertilization and c ell fate determination(8-11) to disease resistance(12,13) have been modelle d in A. thaliana, identifying mutations in this organism has been impeded b y the lack of a high-density genetic: map consisting of easily genotyped DN A markers(14). We report here the construction of a biallelic genetic map i n A. thaliana with a resolution of 3.5 cM and its use in mapping Eds16, a g ene involved in the defence response to the fungal pathogen Erysiphe oronti i. Mapping of this trait involved the high-throughput generation of meiotic maps of F-2 individuals using high-density oligonucleotide probe array-bas ed genotyping. We developed a software package called InterMap and used it to automatically delimit Eds16 to a 7-cM interval on chromosome 1. These re sults are the first demonstration of biallelic mapping in diploid genomes a nd establish means for generalizing SNP-based maps to virtually any genetic organism.