Title Population-and genome-specific patterns of linkage disequilibrium and SNP variation in spring and winter wheat ( Triticum aestivum L . ) Permalink

Background: Single nucleotide polymorphisms (SNPs) are ideally suited for the construction of high-resolution genetic maps, studying population evolutionary history and performing genome-wide association mapping experiments. Here, we used a genome-wide set of 1536 SNPs to study linkage disequilibrium (LD) and population structure in a panel of 478 spring and winter wheat cultivars (Triticum aestivum) from 17 populations across the United States and Mexico. Results: Most of the wheat oligo pool assay (OPA) SNPs that were polymorphic within the complete set of 478 cultivars were also polymorphic in all subpopulations. Higher levels of genetic differentiation were observed among wheat lines within populations than among populations. A total of nine genetically distinct clusters were identified, suggesting that some of the pre-defined populations shared significant proportion of genetic ancestry. Estimates of population structure (FST) at individual loci showed a high level of heterogeneity across the genome. In addition, seven genomic regions with elevated FST were detected between the spring and winter wheat populations. Some of these regions overlapped with previously mapped flowering time QTL. Across all populations, the highest extent of significant LD was observed in the wheat D-genome, followed by lower LD in the Aand B-genomes. The differences in the extent of LD among populations and genomes were mostly driven by differences in long-range LD ( > 10 cM). Conclusions: Genomeand population-specific patterns of genetic differentiation and LD were discovered in the populations of wheat cultivars from different geographic regions. Our study demonstrated that the estimates of population structure between spring and winter wheat lines can identify genomic regions harboring candidate genes involved in the regulation of growth habit. Variation in LD suggests that breeding and selection had a different impact on each wheat genome both within and among populations. The higher extent of LD in the wheat D-genome versus the Aand B-genomes likely reflects the episodes of recent introgression and population bottleneck accompanying the origin of hexaploid wheat. The assessment of LD and population structure in this assembled panel of diverse lines provides critical information for the development of genetic resources for genome-wide association mapping of agronomically important traits in wheat. * Correspondence: eakhunov@ksu.edu Department of Plant Pathology, Kansas State University, Manhattan, KS, USA Full list of author information is available at the end of the article Chao et al. BMC Genomics 2010, 11:727 http://www.biomedcentral. com/1471-2164/11/727 © 2010 Chao et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background In crops, the level of genetic diversity and linkage disequilibrium (LD) can be affected by various factors including demography and inbreeding [1-6], selection for favorable alleles [7,8], domestication [2,9,10], outcrossing of crop cultivars with genetically distinct lines of wild ancestors and landraces [1,11,12] and admixture [13,14]. Genetic diversity of domesticated crops is usually reduced compared to wild ancestors [2,6,9,15,16]. In tetraploid wheat, the population bottleneck that accompanied tetraploid emmer wheat domestication about 10,000 years ago [17] reduced nucleotide diversity by 30 to 50% in the Aand B-genomes, depending on the study and diversity measure used [15,18]. Diversity was further reduced in hexaploid wheat as a consequence of the polyploidy bottleneck resulting from hexaploid wheat speciation [18,19]. Different rates of gene flow from the ancestors of hexaploid wheat, tetraploid wheat for the Aand B-genomes and Aegilops tauschii for the D-genome [20,21] resulted in different levels of diversity in hexaploid wheat genomes [19]. While diversity levels are similar in the Aand B-genomes, it is greatly reduced in the D-genome [18,19]. The D-genome also shows higher levels of LD than the Aand B-genomes [19,22]. Interpreting patterns of genetic diversity in modern crop cultivars is further complicated by strong selection and interbreeding with landraces and genetically distant wild relatives. Regions of the genome subjected to recent selection or introgressions from landraces or wild relatives were shown to have elevated LD and low genetic diversity [7,12,23]. Factors such as inbreeding, humanand environment-driven selection, founder effect and gene flow influence the distribution of genetic variation both across the genome and between populations resulting in the formation of genetically differentiated groups [2-6]. Strong population structure has been reported for many crops including wheat [5,22,24,25]. A thorough understanding of population structure has important implications as population structure is one of the major reasons for false associations between phenotypes and markers in association mapping (AM) studies [26]. Hence, the inclusion of population structure estimates in AM is important for reducing spurious associations [27]. On the practical level, the distribution of genetic diversity in modern cultivars plays an important role in the choice of specific mapping and crop improvement strategies. In recent years, association mapping was shown to be a powerful method for complementing the traditional gene mapping studies based on controlled crosses [5,28-30]. The extent of LD defines the marker density required for genome-wide association mapping (GWAM). GWAM experiments in human and natural plant populations require several hundred thousand SNPs for finding a marker allele linked to a causal mutation [4,31]. However, the elevated level of LD in crop populations suggests that a smaller number of markers can provide sufficient genome coverage for finding marker-trait associations. Indeed, in two-row spring barley cultivars significant intra-chromosomal LD extended up to 15 cM [3]. Analysis of LD patterns in U. S. wheat populations showed significant LD extended to 5 cM [25] or 10 cM [22] while some populations of durum wheat (T. turgidum) retained more than 50% of their initial LD value at distances up to 20 cM [24]. In theory, by selecting a set of closely related cultivars it should be possible to increase the extent of LD and use fewer markers for detecting associations. Recent advances in DNA sequencing and genotyping have enabled genome-wide studies capable of characterizing genetic variation and the extent of LD in natural and breeding populations. Single nucleotide polymorphism (SNP) has become the most frequently used type of molecular marker for these analyses in many species because of their high abundance across the genome and the availability of cost-effective high-throughput genotyping assays [32-34]. One of the first sets of SNPs developed for polyploid wheat [19] was used in this study to design a 1536-plex wheat oligo pool assay (wheat OPA) to analyze the patterns of SNP variation and LD in diverse populations of cultivated spring and winter wheat lines from the US and CIMMYT ("Centro Internacional de Mejoramiento de Maíz y Trigo”) breeding programs. This knowledge is critical to the design of valid GWAM experiments in wheat and useful for understanding the role of selection and breeding in the distribution of genetic variation across the wheat genome.