Abstract
Recombinant populations were the basis for Mendel's first genetic experiments and continue to be key to the study of genes, heredity, and genetic variation today. Genotyping several hundred thousand loci in a single assay by hybridizing genomic DNA to oligonucleotide arrays provides a powerful technique to improve precision linkage mapping. The genotypes of two accessions of Arabidopsis were compared by using a 400,000 feature exon-specific oligonucleotide array. Around 16,000 single feature polymorphisms (SFPs) were detected in ~8,000 of the ~26,000 genes represented on the array. Allelic variation at these loci was measured in a recombinant inbred line population, which defined the location of 815 recombination breakpoints. The genetic linkage map had a total length of 422.5 cM, with 676 informative SFP markers representing intervals of ~0.6 cM. One hundred fifteen single gene intervals were identified. Recombination rate, SFP distribution, and segregation in this population are not uniform. Many genomic regions show a clustering of recombination events including significant hot spots. The precise haplotype structure of the recombinant population was defined with unprecedented accuracy and resolution. The resulting linkage map allows further refinement of the hundreds of quantitative trait loci identified in this well-studied population. Highly variable recombination rates along each chromosome and extensive segregation distortion were observed in the population.
Highlights
A key discovery of classical genetics was the observation that some phenotypes do not segregate independently and are physically linked, making it possible to map a gene to a location on a chromosome
Depending on the significance threshold, we identified 20,450 single feature polymorphisms (SFPs) (FDR 1⁄4 0.05) corresponding to 7,920 genes (Table 1, Table S1), or 15,928 SFPs (FDR 1⁄4 0.01) corresponding to 6,600 genes (Table 1, Table S2, and Figure S1)
4–5% of all features on the array resulted in an SFP, that is, one SFP was identified for approximately one-third of all genes, occurring on average every 9 kb (Table S4)
Summary
A key discovery of classical genetics was the observation that some phenotypes do not segregate independently and are physically linked, making it possible to map a gene to a location on a chromosome. In an organism with an annotated genome sequence, linkage analysis goes beyond associating traits and discrete molecular markers: the molecular markers and traits co-segregate with known and characterized genomic regions. That is, the size of the region confidently associated with a trait, is a function of marker density, recombination rate, and the proportion of the phenotypic variation due to genetic factors. Technological advances have made it possible to genotype several hundred thousand loci in a single assay by hybridizing DNA to a high-density oligonucleotide array. This approach has been reported in yeast [1], Plasmodium [2], Anopheles [3], human [4], and Arabidopsis [5]. When integrated with a completely sequenced genome, the exact genomic location of each feature is known, adding to the utility of the marker
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