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Genetics, Vol. 168, 1627-1638, November 2004, Copyright © 2004
doi:10.1534/genetics.104.029470

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Haplotype Structure and Phenotypic Associations in the Chromosomal Regions Surrounding Two Arabidopsis thaliana Flowering Time Loci

Jenny Hagenblad*,1,2, Chunlao Tang*,1, John Molitor{dagger}, Jonathan Werner{ddagger}, Keyan Zhao*, Honggang Zheng*, Paul Marjoram{dagger}, Detlef Weigel{ddagger},§ and Magnus Nordborg*,3

* Molecular and Computational Biology Program, University of Southern California, Los Angeles, California 90089
{dagger} Department of Preventive Medicine, University of Southern California, Los Angeles, California 90089
{ddagger} Plant Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037
§ Max Planck Institute for Developmental Biology, D-72076 Tübingen, Germany

3 Corresponding author: Molecular and Computational Biology, University of Southern California, 835 W 37th St., SHS 172, Los Angeles, CA 90089-1340.
E-mail: magnus{at}usc.edu

The feasibility of using linkage disequilbrium (LD) to fine-map loci underlying natural variation in Arabidopsis thaliana was investigated by looking for associations between flowering time and marker polymorphism in the genomic regions containing two candidate genes, FRI and FLC, both of which are known to contribute to natural variation in flowering. A sample of 196 accessions was used, and polymorphism was assessed by sequencing a total of 17 roughly 500-bp fragments. Using a novel Bayesian algorithm based on haplotype similarity, we demonstrate that LD could have been used to fine-map the FRI gene to a roughly 30-kb region and to identify two common loss-of-function alleles. Interestingly, because of genetic heterogeneity, simple single-marker associations would not have been able to map FRI with nearly the same precision. No clear evidence for previously unknown alleles at either locus was found, but the effect of population structure in causing false positives was evident.




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