Analysis of molecular diversity,population structure and linkage disequilibrium in a worldwide survey of cultivated barley germplasm (<Emphasis Type="Italic">Hordeum vulgare</Emphasis> L.)

Background

The goal of our study was a systematic survey of the molecular diversity in barley genetic resources. To this end 953 cultivated barley accessions originating from all inhabited continents except Australia were genotyped with 48 SSR markers. Molecular diversity was evaluated with routine statistics (allelic richness, gene diversity, allele frequency, heterozygosity and unique alleles), Principal Coordinate Analysis (PCoA), and analysis of genome-wide linkage disequilibrium.

Results

A genotyping database for 953 cultivated barley accessions profiled with 48 SSR markers was established. The PCoA revealed structuring of the barley population with regard to (i) geographical regions and (ii) agronomic traits. Geographic origin contributed most to the observed molecular diversity. Genome-wide linkage disequilibrium (LD) was estimated as squared correlation of allele frequencies (r²). The values of LD for barley were comparable to other plant species (conifers, poplar, maize). The pattern of intrachromosomal LD with distances between the genomic loci ranging from 1 to 150 cM revealed that in barley LD extended up to distances as long as 50 cM with r² > 0.05, or up to 10 cM with r² > 0.2. Few loci mapping to different chromosomes showed significant LD with r² > 0.05. The number of loci in significant LD as well as the pattern of LD were clearly dependent on the population structure. The LD in the homogenous group of 207 European 2-rowed spring barleys compared to the highly structured worldwide barley population was increased in the number of loci pairs with r² > 0.05 and had higher values of r², although the percentage of intrachromosomal loci pairs in significant LD based on P < 0.001 was 100% in the whole set of varieties, but only 45% in the subgroup of European 2-rowed spring barleys. The value of LD also varied depending on the polymorphism of the loci selected for genotyping. The 17 most polymorphic loci (PIC > 0.80) provided higher LD values as compared to 19 low polymorphic loci (PIC < 0.73) in both structured (all accessions) and non-structured (European 2-rowed spring varieties) barley populations.

Conclusion

A global population of cultivated barley accessions was highly structured. Clustering highlighted the accessions with the same geographic origin, as well as accessions possessing similar agronomic characters. LD in barley extended up to 50 cM, and was strongly dependent on the population structure. The data on LD were summarized as a genome-wide LD map for barley.

     

Molecular diversity and association mapping of fiber quality traits in exotic G. hirsutum L. germplasm

The narrow genetic base of cultivated cotton germplasm is hindering the cotton productivity worldwide. Although potential genetic diversity exists in Gossypium genus, it is largely ‘underutilized’ due to photoperiodism and the lack of innovative tools to overcome such challenges. The application of linkage disequilibrium (LD)-based association mapping is an alternative powerful molecular tool to dissect and exploit the natural genetic diversity conserved within cotton germplasm collections, greatly accelerating still ‘lagging’ cotton marker-assisted selection (MAS) programs. However, the extent of genome-wide linkage disequilibrium (LD) has not been determined in cotton. We report the extent of genome-wide LD and association mapping of fiber quality traits by using a 95 core set of microsatellite markers in a total of 285 exotic Gossypium hirsutum accessions, comprising of 208 landrace stocks and 77 photoperiodic variety accessions. We demonstrated the existence of useful genetic diversity within exotic cotton germplasm. In this germplasm set, 11–12% of SSR loci pairs revealed a significant LD. At the significance threshold (r² ≥ 0.1), a genome-wide average of LD declines within the genetic distance at < 10 cM in the landrace stocks germplasm and > 30 cM in variety germplasm. Genome wide LD at r² ≥ 0.2 was reduced on average to  1–2 cM in the landrace stock germplasm and 6–8 cM in variety germplasm, providing evidence of the potential for association mapping of agronomically important traits in cotton. We observed significant population structure and relatedness in assayed germplasm. Consequently, the application of the mixed liner model (MLM), considering both kinship (K) and population structure (Q) detected between 6% and 13% of SSR markers associated with the main fiber quality traits in cotton. Our results highlight for the first time the feasibility and potential of association mapping, with consideration of the population structure and stratification existing in cotton germplasm resources. The number of SSR markers associated with fiber quality traits in diverse cotton germplasm, which broadly covered many historical meiotic events, should be useful to effectively exploit potentially new genetic variation by using MAS programs.     

Construction of an RFLP linkage map for cultivated sunflower

 An RFLP linkage map was constructed for cultivated sunflower Helianthus annuus L., based on 271 loci detected by 232 cDNA probes. Ninety-three F₂ plants of a cross between inbred lines RHA 271 and HA 234 were used as the mapping population. These genetic markers plus a fertility restoration gene, Rf ₁, defined 20 linkage groups, covering 1164 cM of the sunflower genome. Of the 71 loci 202 had codominant genotypic segregation, with the rest showing dominant segregation. Thirty-two of the 232 probes gave multiple locus segregation. There were 39 clusters of tightly linked markers with 0 cM distance among loci. This map has an average marker-to-marker distance of 4.6 cM, with 11 markerless regions exceeding 20 cM. Received: 17 June 1997 / Accepted: 19 June 1997     

Linkage disequilibrium and sequence diversity in a 500-kbp region around the adh1 locus in elite maize germplasm

Linkage disequilibrium (LD) at the adh1 locus was examined in two sets of maize inbreds. A set of 32 was chosen to represent most of the genetic diversity in the cultivated North American elite maize breeding pool. A second set of 192 inbreds was chosen to sample more deeply the two major heterotic groups in elite maize germplasm. Analysis of several loci in the vicinity of the adh1 gene shows that LD as measured by D and r² extends greater than 500 kbp in this germplasm. The presence of this exceptionally long segment of high LD may be suggestive of selection acting on one of the genes in the vicinity of adh1 or of a locally reduced rate of recombination.Electronic Supplementary Material Supplementary material is available for this article at .     

Population structure and linkage disequilibrium in oat (<Emphasis Type="Italic">Avena sativa</Emphasis> L.): implications for genome-wide association studies

The level of population structure and the extent of linkage disequilibrium (LD) can have large impacts on the power, resolution, and design of genome-wide association studies (GWAS) in plants. Until recently, the topics of LD and population structure have not been explored in oat due to the lack of a high-throughput, high-density marker system. The objectives of this research were to survey the level of population structure and the extent of LD in oat germplasm and determine their implications for GWAS. In total, 1,205 lines and 402 diversity array technology (DArT) markers were used to explore population structure. Principal component analysis and model-based cluster analysis of these data indicated that, for the lines used in this study, relatively weak population structure exists. To explore LD decay, map distances of 2,225 linked DArT marker pairs were compared with LD (estimated as r ²). Results showed that LD between linked markers decayed rapidly to r ² = 0.2 for marker pairs with a map distance of 1.0 centi-Morgan (cM). For GWAS, we suggest a minimum of one marker every cM, but higher densities of markers should increase marker-QTL association and therefore detection power. Additionally, it was found that LD was relatively consistent across the majority of germplasm clusters. These findings suggest that GWAS in oat can include germplasm with diverse origins and backgrounds. The results from this research demonstrate the feasibility of GWAS and related analyses in oat.     

Linkage Disequilibrium in Salt Tolerant Genotypes of Rice (Oryza sativa L)

Genome wide linkage disequilibrium (LD) was investigated in a set of 32 genotypes representing salt tolerant improved varieties and landraces and six salt sensitive genotypes of rice with 64 microsatellite markers to identify the genomic regions that are associated with salt tolerance in rice. Out of 64 markers analyzed, 36% SSR pairs exhibited significant LD at 0.05. A few regions were identified as targets of selection in 10 chromosomes with high r ² values. The model-based groups from Bayesian clustering analysis are largely consistent with known pedigrees of the lines. The increased percentage of association of SSR loci in the improved varieties indicated the role of selection in linkage disequilibrium especially for salt tolerance. LD was extended as far as 100 cM in the present study. Most of the markers (43.8%) with significant LD values were observed in the genomic regions of reported QTL for salt tolerance in rice.     

Patterns of genetic diversity and linkage disequilibrium in a highly structured Hordeum vulgare association-mapping population for the Mediterranean basin

Population structure and genome-wide linkage disequilibrium (LD) were investigated in 192 Hordeum vulgare accessions providing a comprehensive coverage of past and present barley breeding in the Mediterranean basin, using 50 nuclear microsatellite and 1,130 DArT^® markers. Both clustering and principal coordinate analyses clearly sub-divided the sample into five distinct groups centred on key ancestors and regions of origin of the germplasm. For given genetic distances, large variation in LD values was observed, ranging from closely linked markers completely at equilibrium to marker pairs at 50 cM separation still showing significant LD. Mean LD values across the whole population sample decayed below r ² of 0.15 after 3.2 cM. By assaying 1,130 genome-wide DArT^® markers, we demonstrated that, after accounting for population substructure, current genome coverage of 1 marker per 1.5 cM except for chromosome 4H with 1 marker per 3.62 cM is sufficient for whole genome association scans. We show, by identifying associations with powdery mildew that map in genomic regions known to have resistance loci, that associations can be detected in strongly stratified samples provided population structure is effectively controlled in the analysis. The population we describe is, therefore, shown to be a valuable resource, which can be used in basic and applied research in barley.     

Linkage disequilibrium and extended haplotypes in the HLA-A to D6S105 region: implications for mapping the hemochromatosis gene (HFE)

The hemochromatosis gene (HFE) maps to 6p21.3, in close linkage with the HLA Class I genes. Linkage disequilibrium (LD) studies were designed to narrow down the most likely candidate region for HFE, as an alternative to traditional linkage analysis. However, both the HLA-A and D6S105 subregions, which are situated 2–3 cM and approximately 3 Mb apart, have been suggested to contain HFE. The present report extends our previous study based upon the analysis of a large number of HFE and normal chromosomes from 66families of Breton ancestry. In addition to the previously used RFLP markers spanning the 400-kb surrounding HLA-A, we examined three microsatellites: D6S510, HLA-F, and D6S105. Our combined data not only confirm a peak of LD at D6S105, but also reveal a complex pattern of LD over the i82 to D6S105 interval. Within our ethnically well-defined population of Brittany, the association of HFE with D6S105 is as great as that with HLA-A, while the internal markers display a lower LD. Fine haplotype analysis enabled us to identify two categories of haplotypes segregating with HFE. In contrast to the vast majority of normal haplotypes, 50% of HFE haplotypes are completely conserved over the HLA-A to D6S105 interval. These haplotypes could have been conserved through recombination suppression, selective forces and/or other evolutionary factors. This particular haplotypic configuration might account for the apparent inconsistencies between genetic linkage and LD data, and additionally greatly complicates positional cloning of HFE through disequilibrium mapping.The authors contributed equally to this work     

Linkage disequilibrium based association mapping of fiber quality traits in <Emphasis Type="Italic">G. hirsutum</Emphasis> L. variety germplasm

Cotton is the world’s leading cash crop, but it lags behind other major crops for marker-assisted breeding due to limited polymorphisms and a genetic bottleneck through historic domestication. This underlies a need for characterization, tagging, and utilization of existing natural polymorphisms in cotton germplasm collections. Here we report genetic diversity, population characteristics, the extent of linkage disequilibrium (LD), and association mapping of fiber quality traits using 202 microsatellite marker primer pairs in 335 G. hirsutum germplasm grown in two diverse environments, Uzbekistan and Mexico. At the significance threshold (r ² ≥ 0.1), a genome-wide average of LD extended up to genetic distance of 25 cM in assayed cotton variety accessions. Genome wide LD at r ² ≥ 0.2 was reduced to ~5–6 cM, providing evidence of the potential for association mapping of agronomically important traits in cotton. Results suggest linkage, selection, inbreeding, population stratification, and genetic drift as the potential LD-generating factors in cotton. In two environments, an average of ~20 SSR markers was associated with each main fiber quality traits using a unified mixed liner model (MLM) incorporating population structure and kinship. These MLM-derived significant associations were confirmed in general linear model and structured association test, accounting for population structure and permutation-based multiple testing. Several common markers, showing the significant associations in both Uzbekistan and Mexican environments, were determined. Between 7 and 43% of the MLM-derived significant associations were supported by a minimum Bayes factor at ‘moderate to strong’ and ‘strong to very strong’ evidence levels, suggesting their usefulness for marker-assisted breeding programs and overall effectiveness of association mapping using cotton germplasm resources. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Population structure and linkage disequilibrium unravelled in tetraploid potato

Association mapping is considered to be an important alternative strategy for the identification of quantitative trait loci (QTL) as compared to traditional QTL mapping. A necessary prerequisite for association analysis to succeed is detailed information regarding hidden population structure and the extent of linkage disequilibrium. A collection of 430 tetraploid potato cultivars, comprising two association panels, has been analysed with 41 AFLP^® and 53 SSR primer combinations yielding 3364 AFLP fragments and 653 microsatellite alleles, respectively. Polymorphism information content values and detected number of alleles for the SSRs studied illustrate that commercial potato germplasm seems to be equally diverse as Latin American landrace material. Genome-wide linkage disequilibrium (LD)—reported for the first time for tetraploid potato—was observed up to approximately 5 cM using r ² higher than 0.1 as a criterion for significant LD. Within-group LD, however, stretched on average twice as far when compared to overall LD. A Bayesian approach, a distance-based hierarchical clustering approach as well as principal coordinate analysis were adopted to enquire into population structure. Groups differing in year of market release and market segment (starch, processing industry and fresh consumption) were repeatedly detected. The observation of LD up to 5 cM is promising because the required marker density is not likely to disable the possibilities for association mapping research in tetraploid potato. Population structure appeared to be weak, but strong enough to demand careful modelling of genetic relationships in subsequent marker-trait association analyses. There seems to be a good chance that linkage-based marker-trait associations can be identified at moderate marker densities.     

An expressed sequence tag SSR map of tetraploid alfalfa (Medicago sativa L.)

A genetic map constructed from a population segregating for a trait of interest is required for QTL identification. The goal of this study was to construct a molecular map of tetraploid alfalfa (Medicago sativa.) using simple sequence repeat (SSR) markers derived primarily from expressed sequence tags (ESTs) and bacterial artificial chromosome (BAC) inserts of M. truncatula. This map will be used for the identification of drought tolerance QTL in alfalfa. Two first generation backcross populations were constructed from a cross between a water-use efficient, M. sativa subsp. falcata genotype and a low water-use efficient M. sativa subsp. sativa genotype. The two parents and their F₁ were screened with 1680 primer pairs designed to amplify SSRs, and 605 single dose alleles (SDAs) were amplified. In the F₁, 351 SDAs from 256 loci were mapped to 41 linkage groups. SDAs not inherited by the F₁, but transmitted through the recurrent parents and segregating in the backcross populations, were mapped to 43 linkage groups, and 44 of these loci were incorporated into the composite maps. Homologous linkage groups were joined to form eight composite linkage groups representing the eight chromosomes of M. sativa. The composite maps consist of eight composite linkage groups with 243 SDAs from M. truncatula EST sequences, 38 SDAs from M. truncatula BAC clone sequences, and five SDAs from alfalfa genomic SSRs. The total composite map length is 624 cM, with average marker density per composite linkage group ranging from 1.5 to 4.4 cM, and an overall average density of 2.2 cM. Segregation distortion was 10%, and distorted loci tended to cluster on individual homologues of several linkage groups. Electronic Supplementary Material Supplementary material is available for this article at     

Prospects for whole genome linkage disequilibrium mapping in domestic dog breeds

Linkage disequilibrium (LD) mapping is commonly used as a fine mapping tool in human genome mapping and has been used with some success for initial disease gene isolation in certain isolated inbred human populations. An understanding of the population history of domestic dog breeds suggests that LD mapping could be routinely utilized in this species for initial genome-wide scans. Such an approach offers significant advantages over traditional linkage analysis. Here, we demonstrate, using canine copper toxicosis in the Bedlington terrier as the model, that LD mapping could be reasonably expected to be a useful strategy in low-resolution, genome-wide scans in pure-bred dogs. Significant LD was demonstrated over distances up to 33.3 cM. It is very unlikely, for a number of reasons discussed, that this result could be extrapolated to the rest of the genome. It is, however, consistent with the expectation given the population structure of canine breeds and, in this breed at least, with the hypothesis that it may be possible to utilize LD in a genome-wide scan. In this study, LD mapping confirmed the location of the copper toxicosis in Bedlington terrier gene (CT-BT) and was able to do so in a population that was refractory to traditional linkage analysis.     

Genetic variation, population structure, and linkage disequilibrium in European elite germplasm of perennial ryegrass

Perennial ryegrass (Lolium perenne L.) is a highly valued temperate climate grass species grown as forage crop and for amenity uses. Due to its outbreeding nature and recent domestication, a high degree of genetic diversity is expected among cultivars. The aim of this study was to assess the extent of linkage disequilibrium (LD) within European elite germplasm and to evaluate the appropriate methodology for genetic association mapping in perennial ryegrass. A high level of genetic diversity was observed in a set of 380 perennial ryegrass elite genotypes when genotyped with 40 SSRs and 2 STS markers. A Bayesian structure analysis identified two subpopulations, which were confirmed by principal coordinate analysis (PCoA). One subpopulation consisted mainly of genotypes originating from the UK, while germplasm mostly from Continental Europe was grouped into the second subpopulation. LD (r²) decay was rapid and occurred within 0.4 cM across European varieties, when population structure was taken into consideration. However, an extended LD of up to 6.6 cM was detected within the variety Aberdart. High genetic diversity and rapid LD decay provide means for high resolution association mapping in elite materials of perennial ryegrass. However, different strategies need to be applied depending on the material used. Genome-wide association study (GWAS) with several hundred markers can be applied within synthetic varieties to identify large (up to 10 cM) genomic regions affecting trait variation. A combination of available and novel DNA markers is needed to achieve resolution required for GWAS in elite breeding materials. An even higher marker density of several million SNPs might be needed for GWAS in diverse ecotype collections, potentially resulting in quantitative trait polymorphism (QTP) identification.     

Population structure and linkage disequilibrium in barley assessed by DArT markers

Diversity Array Technology (DArT) markers were used to investigate the genetic diversity, population structure, and extent of linkage disequilibrium (LD) on a genome-wide level in Canadian barley (Hordeum vulgare L.). Approximately 1,000 DArT markers were polymorphic and scored with high confidence among a collection of 170 barley lines composed mostly of Canadian cultivars and breeding lines. The reproducibility of DArT markers proved very high, as 99.9% of allele calls were identical among seven replicated samples. The polymorphism information content (PIC) of DArT markers ranged between 0.04 and 0.50 with an average of 0.38. Using principal coordinate analysis (PCoA), most lines fell into one of two major groups reflecting inflorescence type (two-row versus six-row). Within these two large groups, evidence of geographic clustering of genotypes was also observed. A cluster analysis Unweighted Pair Group Method with Algorithmic Mean suggested the existence of three subgroups within the two-row group and four subgroups within the six-row group. An analysis of molecular variance (AMOVA) revealed highly significant (P < 0.001) genetic variance within subgroups, among subgroups, and among groups. Values of LD, expressed as r ², declined with increasing genetic distance, and mean values of r ² fell below 0.2 for markers located 2.6 cM apart. Approximately 8% of marker pairs located on the same chromosome and 3.4% of pairs located on different chromosomes were in LD (r ²  > 0.2). Within both the subsets of two-row and six-row lines, LD extended slightly further (3.5 cM) than for the entire set, while 7.5% of intra-chromosomal locus pairs and <2% of inter-chromosomal pairs were in LD. We discuss the implications of these findings with regard to the prospects of association mapping of complex traits in barley.     

Mapping and linkage disequilibrium analysis with a genome-wide collection of SNPs that detect polymorphism in cultivated tomato

The history of tomato (Solanum lycopersicum L.) improvement includes genetic bottlenecks, wild species introgressions, and divergence into distinct market classes. This history makes tomato an excellent model to investigate the effects of selection on genome variation. A combination of linkage mapping in two F(2) populations and physical mapping with emerging genome sequence data was used to position 434 PCR-based markers including SNPs. Three-hundred-and-forty markers were used to genotype 102 tomato lines representing wild species, landraces, vintage cultivars, and contemporary (fresh market and processing) varieties. Principal component analysis confirmed genetic divergence between market classes of cultivated tomato (P <0.0001). A genome-wide survey indicated that linkage disequilibrium (LD) decays over 6-8 cM when all cultivated tomatoes, including vintage and contemporary, were considered together. Within contemporary processing varieties, LD decayed over 6-14 cM, and decay was over 3-16 cM within fresh market varieties. Significant inter-chromosomal (gametic phase) LD was detected in both fresh market and processing varieties between chromosomes 2 and 3, and 2 and 4, but in distinct chromosomal locations for each market class. Additional LD was detected between chromosomes 3 and 4, 3 and 11, and 4 and 6 in fresh market varieties and chromosomes 3 and 12 in processing varieties. These results suggest that breeding practices for market specialization in tomato have led to a genetic divergence between fresh market and processing types.     

The pattern of linkage disequilibrium in German Holstein cattle

This study presents a second generation of linkage disequilibrium (LD) map statistics for the whole genome of the Holstein–Friesian population, which has a four times higher resolution compared with that of the maps available so far. We used DNA samples of 810 German Holstein–Friesian cattle genotyped by the Illumina Bovine SNP50K BeadChip to analyse LD structure. A panel of 40 854 (75.6%) markers was included in the final analysis. The pairwise r² statistic of SNPs up to 5 Mb apart across the genome was estimated. A mean value of r² = 0.30 ± 0.32 was observed in pairwise distances of <25 kb and it dropped to 0.20 ± 0.24 at 50–75 kb, which is nearly the average inter‐marker space in this study. The proportion of SNPs in useful LD (r² ≥ 0.25) was 26% for the distance of 50 and 75 kb between SNPs. We found a lower level of LD for SNP pairs at the distance ≤100 kb than previously thought. Analysis revealed 712 haplo‐blocks spanning 4.7% of the genome and containing 8.0% of all SNPs. Mean and median block length were estimated as 164 ± 117 kb and 144 kb respectively. Allele frequencies of the SNPs have a considerable and systematic impact on the estimate of r². It is shown that minimizing the allele frequency difference between SNPs reduces the influence of frequency on r² estimates. Analysis of past effective population size based on the direct estimates of recombination rates from SNP data showed a decline in effective population size to N_e = 103 up to ～4 generations ago. Systematic effects of marker density and effective population size on observed LD and haplotype structure are discussed.     

A first insight into population structure and linkage disequilibrium in the US peanut minicore collection

Knowledge of genetic diversity, population structure, and degree of linkage disequilibrium (LD) in target association mapping populations is of great importance and is a prerequisite for LD-based mapping. In the present study, 96 genotypes comprising 92 accessions of the US peanut minicore collection, a component line of the tetraploid variety Florunner, diploid progenitors A. duranensis (AA) and A. ipaënsis (BB), and synthetic amphidiploid accession TxAG-6 were investigated with 392 simple sequence repeat (SSR) marker bands amplified using 32 highly-polymorphic SSR primer pairs. Both distance- and model-based (Bayesian) cluster analysis revealed the presence of structured diversity. In general, the wild-species accessions and the synthetic amphidiploid grouped separately from most minicore accessions except for COC155, and were eliminated from most subsequent analyses. UPGMA analysis divided the population into four subgroups, two major subgroups representing subspecies fastigiata and hypogaea, a third group containing individuals from each subspecies or possibly of mixed ancestry, and a fourth group, either consisting of COC155 alone if wild species were excluded, or of COC155, the diploid species, and the synthetic amphidiploid. Model-based clustering identified four subgroups- one each for fastigiata and hypogaea subspecies, a third consisting of individuals of both subspecies or of mixed ancestry predominantly from Africa or Asia, and a fourth group, consisting of individuals predominantly of var fastigiata, peruviana, and aequatoriana accessions from South America, including COC155. Analysis of molecular variance (AMOVA) revealed statistically-significant (P < 0.0001) genetic variance of 16.87% among subgroups. A total of 4.85% of SSR marker pairs revealed significant LD (at r² ≥ 0.1). Of the syntenic marker pairs separated by distances < 10 cM, 11–20 cM, 21–50 cM, and > 50 cM, 19.33, 5.19, 6.25 and 5.29% of marker pairs were found in strong LD (P ≤ 0.01), in accord with LD extending to great distances in self pollinated crops. A threshold value of r² > 0.035 was found to distinguish mean r² values of linkage distance groups statistically from the mean r² values of unlinked markers; LD was found to extend to 10 cM over the entire minicore collection by this criterion. However, there were large differences in r² values among marker pairs even among tightly-linked markers. The implications of these findings with regard to the possibility of using association mapping for detection of genome-wide SSR marker-phenotype association are discussed.     

Evaluation of LD decay and various LD-decay estimators in simulated and SNP-array data of tetraploid potato

Key message

The number of SNPs required for QTL discovery is justified by the distance at which linkage disequilibrium has decayed. Simulations and real potato SNP data showed how to estimate and interpret LD decay.

Abstract

The magnitude of linkage disequilibrium (LD) and its decay with genetic distance determine the resolution of association mapping, and are useful for assessing the desired numbers of SNPs on arrays. To study LD and LD decay in tetraploid potato, we simulated autotetraploid genotypes and used it to explore the dependence on: (1) the number of haplotypes in the population (the amount of genetic variation) and (2) the percentage of haplotype specific SNPs (hs-SNPs). Several estimators for short-range LD were explored, such as the average r ², median r ², and other percentiles of r ² (80, 90, and 95 %). For LD decay, we looked at LD_½,90, the distance at which the short-range LD is halved when using the 90 % percentile of r ² at short range, as estimator for LD. Simulations showed that the performance of various estimators for LD decay strongly depended on the number of haplotypes, although the real value of LD decay was not influenced very much by this number. The estimator LD_½,90 was chosen to evaluate LD decay in 537 tetraploid varieties. LD_½,90 values were 1.5 Mb for varieties released before 1945 and 0.6 Mb in varieties released after 2005. LD_½,90 values within three different subpopulations ranged from 0.7 to 0.9 Mb. LD_½,90 was 2.5 Mb for introgressed regions, indicating large haplotype blocks. In pericentromeric heterochromatin, LD decay was negligible. This study demonstrates that several related factors influencing LD decay could be disentangled, that no universal approach can be suggested, and that the estimation of LD decay has to be performed with great care and knowledge of the sampled material.

     

FastTagger: an efficient algorithm for genome-wide tag SNP selection using multi-marker linkage disequilibrium

Background  

Human genome contains millions of common single nucleotide polymorphisms (SNPs) and these SNPs play an important role in understanding the association between genetic variations and human diseases. Many SNPs show correlated genotypes, or linkage disequilibrium (LD), thus it is not necessary to genotype all SNPs for association study. Many algorithms have been developed to find a small subset of SNPs called tag SNPs that are sufficient to infer all the other SNPs. Algorithms based on the r ² LD statistic have gained popularity because r ² is directly related to statistical power to detect disease associations. Most of existing r ² based algorithms use pairwise LD. Recent studies show that multi-marker LD can help further reduce the number of tag SNPs. However, existing tag SNP selection algorithms based on multi-marker LD are both time-consuming and memory-consuming. They cannot work on chromosomes containing more than 100 k SNPs using length-3 tagging rules.     

A composite linkage map from two crosses for the species complex Picea mariana × Picea rubens and analysis of synteny with other Pinaceae

Four individual linkage maps were constructed from two crosses for the species complex Picea mariana (Mill.) B.S.P. × Picea rubens Sarg in order to integrate their information into a composite map and to compare with other Pinaceae. For all individual linkage maps, 12 major linkage groups were recovered with 306 markers per map on average. Before building the composite linkage map, the common male parent between the two crosses made it possible to construct a reference linkage map to validate the relative position of homologous markers. The final composite map had a length of 2,319 cM (Haldane) and contained a total of 1,124 positioned markers, including 1,014 AFLPs, 3 RAPDs, 53 SSRs, and 54 ESTPs, assembled into 12 major linkage groups. Marker density of the composite map was statistically homogenous and was much higher (one marker every 2.1 cM) than that of the individual linkage maps (one marker every 5.7 to 7.1 cM). Synteny was well conserved between individual, reference, and composite linkage maps and 94% of homologous markers were colinear between the reference and composite maps. The combined information from the two crosses increased by about 24% the number of anchor markers compared to the information from any single cross. With a total number of 107 anchor markers (SSRs and ESTPs), the composite linkage map is a useful starting point for large-scale genome comparisons at the intergeneric level in the Pinaceae. Comparisons of this map with those in Pinus and Pseudotsuga allowed the identification of one breakdown in synteny where one linkage group homoeologous to both Picea and Pinus corresponded to two linkage groups in Pseudotsuga. Implications for the evolution of the Pinaceae genome are discussed. Electronic Supplementary Material Supplementary material is available for this article at