We have developed a high-throughput genotyping platform by hybridizing genomic DNA from Arabidopsis thaliana accessions to an RNA expression GeneChip (AtGenome1). Using newly developed analytical tools, a large number of single-feature polymorphisms (SFPs) were identified. A comparison of two accessions, the reference strain Columbia (Col) and the strain Landsberg erecta (Ler), identified nearly 4000 SFPs, which could be reliably scored at a 5% error rate. Ler sequence was used to confirm 117 of 121 SFPs and to determine the sensitivity of array hybridization. Features containing sequence repeats, as well as those from high copy genes, showed greater polymorphism rates. A linear clustering algorithm was developed to identify clusters of SFPs representing potential deletions in 111 genes at a 5% false discovery rate (FDR). Among the potential deletions were transposons, disease resistance genes, and genes involved in secondary metabolism. The applicability of this technique was demonstrated by genotyping a recombinant inbred line. Recombination break points could be clearly defined, and in one case delimited to an interval of 29 kb. We further demonstrate that array hybridization can be combined with bulk segregant analysis to quickly map mutations. The extension of these tools to organisms with complex genomes, such as Arabidopsis, will greatly increase our ability to map and clone quantitative trait loci (QTL).[Supplemental material is available online at www.genome.org.]Identifying the molecular basis of natural phenotypic variation will reveal answers to several long-standing evolutionary questions, as well as many important practical problems, not the least of which is the complex genetics of human disease. With the genomics tools now available we have an increased ability to identify functional variants responsible for phenotypic diversity. So far, most complete genome sequences are from model organisms, usually represented by just a single strain. As a consequence, tools such as microarrays are usually designed for that single reference strain. To identify the causes of intraspecific phenotypic variation, we must look beyond reference strains at the whole genome level. By understanding the molecular nature of this diversity we will gain insights into the mechanisms of evolution and discover genes responsible for natural variation. New genomics approaches, applicable to all organisms and strains, need to be developed to assess natural genetic variation at the whole-genome level, allowing us to tap into the diversity that exists outside a handful of laboratory strains.Variation in nature usually takes a continuous quantitative form, contrary to discrete qualitative phenotypes that are typical of laboratory mutations. Quantitative trait locus (QTL) analysis has been used to dissect the polygenic nature of complex traits (Mackay 2001;Mauricio 2001;Doerge 2002). To perform QTL mapping, individuals must be genotyped along all chromosomes. This is often times the limiting step. A method to quickly genotype progen...

Chromosomal inversions are among the primary drivers of genome structure evolution in a wide range of natural populations. While there is an impressive array of theory and empirical analyses that have identified conditions under which inversions can be positively selected, comparatively little data is available on the fitness impacts of these genome structural rearrangements themselves. Because inversion breakpoints can disrupt functional elements and alter chromatin domains, the precise positioning of an inversion’s breakpoints can strongly affect its fitness. Here, we compared the fine-scale distribution of low frequency inversion breakpoints with those of high frequency inversions and inversions that have gone to fixation between Drosophila species. We identified a number of differences among frequency classes that may influence inversion fitness. In particular, breakpoints that are proximal to insulator elements, generate large tandem duplications, and minimize impacts on gene coding spans are more prevalent in high frequency and fixed inversions than in rare inversions. The data suggest that natural selection acts to preserve both genes and larger cis-regulatory networks in the occurrence and spread of rearrangements. These factors may act to limit the availability of high fitness arrangements when suppressed recombination is favorable.

The availability of a complete genome sequence allows the detailed study of intraspecies variability. Here we use high-density oligonucleotide arrays to discover 11,115 single-feature polymorphisms (SFPs) existing in one or more of 14 different yeast strains. We use these SFPs to define regions of genetic identity between common laboratory strains of yeast. We assess the genome-wide distribution of genetic variation on the basis of this yeast population. We find that genome variability is biased toward the ends of chromosomes and is more likely to be found in genes with roles in fermentation or in transport. This subtelomeric bias may arise through recombination between nonhomologous sequences because full-gene deletions are more common in these regions than in more central regions of the chromosome.

Background Whole genome sequencing promises to revolutionize our ability to link genotypic and phenotypic variation in a wide range of model and non-model species. Results Here we describe the isolation and characterization of a novel mycobacteriophage named BGlluviae that grows on Mycobacterium smegmatis mc2155. BGlluviae normally produces turbid plaques but a spontaneous clear plaque was also recovered. The genomic DNA from pure populations of the BGlluviae phage and the clear plaque mutant were sequenced. A single substitution, at amino acid 54 (I to T), in the immunity repressor protein resulted in a clear plaque phenotype. Conclusions This substitution is predicted to be located at the subunit interaction interface of the repressor protein, and thus prevents the establishment of lysogeny.

Chromosomal inversions are among the primary drivers of genome structure evolution in a wide range of natural populations. While there is an impressive array of theory and empirical analyses that has identified conditions under which inversions can be positively selected, comparatively little data is available on the fitness impacts of these genome structural rearrangements themselves. Because inversion breakpoints can interrupt functional elements and alter chromatin domains, each rearrangement may in itself have strong effects on fitness. Here, we compared the fine-scale distribution of low frequency inversion breakpoints with those of high frequency inversions and inversions that have fixed between Drosophila species. We identified important differences that may influence inversion fitness. In particular, proximity to insulator elements, large tandem duplications adjacent to the breakpoints, and minimal impacts on gene coding spans are more prevalent in high frequency and fixed inversions than in rare inversions. The data suggest that natural selection acts both to preserve both genes and larger cis-regulatory networks in the occurrence and spread of rearrangements. These factors may act to limit the availability of high fitness arrangements when suppressed recombination is favorable.