The selfing plant Arabidopsis thaliana has been proposed to be well suited for linkage disequilibrium (LD) mapping as a means of identifying genes underlying natural trait variation. Here we apply LD mapping to examine haplotype variation in the genomic region of the photoperiod receptor CRYPTOCHROME2 and associated flowering time variation. CRY2 DNA sequences reveal strong LD and the existence of two highly differentiated haplogroups (A and B) across the gene; in addition, a haplotype possessing a radical glutamine-to-serine replacement (As) occurs within the more common haplogroup. Growth chamber and field experiments using an unstratified population of 95 ecotypes indicate that under short-day photoperiod, the As and B haplogroups are both highly significantly associated with early flowering. Data from six genes flanking CRY2 indicate that these haplogroups are limited to an ̃65-kb genomic region around CRY2. Whereas the B haplogroup cannot be delimited to <16 kb around CRY2, the As haplogroup is characterized almost exclusively by the nucleotide polymorphisms directly associated with the serine replacement in CRY2; this finding strongly suggests that the serine substitution is directly responsible for the As early flowering phenotype. This study demonstrates the utility of LD mapping for elucidating the genetic basis of natural, ecologically relevant variation in Arabidopsis.
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