26,474 research outputs found

    De novo construction of polyploid linkage maps using discrete graphical models

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    Linkage maps are used to identify the location of genes responsible for traits and diseases. New sequencing techniques have created opportunities to substantially increase the density of genetic markers. Such revolutionary advances in technology have given rise to new challenges, such as creating high-density linkage maps. Current multiple testing approaches based on pairwise recombination fractions are underpowered in the high-dimensional setting and do not extend easily to polyploid species. We propose to construct linkage maps using graphical models either via a sparse Gaussian copula or a nonparanormal skeptic approach. Linkage groups (LGs), typically chromosomes, and the order of markers in each LG are determined by inferring the conditional independence relationships among large numbers of markers in the genome. Through simulations, we illustrate the utility of our map construction method and compare its performance with other available methods, both when the data are clean and contain no missing observations and when data contain genotyping errors and are incomplete. We apply the proposed method to two genotype datasets: barley and potato from diploid and polypoid populations, respectively. Our comprehensive map construction method makes full use of the dosage SNP data to reconstruct linkage map for any bi-parental diploid and polyploid species. We have implemented the method in the R package netgwas.Comment: 25 pages, 7 figure

    netgwas: An R Package for Network-Based Genome-Wide Association Studies

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    Graphical models are powerful tools for modeling and making statistical inferences regarding complex associations among variables in multivariate data. In this paper we introduce the R package netgwas, which is designed based on undirected graphical models to accomplish three important and interrelated goals in genetics: constructing linkage map, reconstructing linkage disequilibrium (LD) networks from multi-loci genotype data, and detecting high-dimensional genotype-phenotype networks. The netgwas package deals with species with any chromosome copy number in a unified way, unlike other software. It implements recent improvements in both linkage map construction (Behrouzi and Wit, 2018), and reconstructing conditional independence network for non-Gaussian continuous data, discrete data, and mixed discrete-and-continuous data (Behrouzi and Wit, 2017). Such datasets routinely occur in genetics and genomics such as genotype data, and genotype-phenotype data. We demonstrate the value of our package functionality by applying it to various multivariate example datasets taken from the literature. We show, in particular, that our package allows a more realistic analysis of data, as it adjusts for the effect of all other variables while performing pairwise associations. This feature controls for spurious associations between variables that can arise from classical multiple testing approach. This paper includes a brief overview of the statistical methods which have been implemented in the package. The main body of the paper explains how to use the package. The package uses a parallelization strategy on multi-core processors to speed-up computations for large datasets. In addition, it contains several functions for simulation and visualization. The netgwas package is freely available at https://cran.r-project.org/web/packages/netgwasComment: 32 pages, 9 figures; due to the limitation "The abstract field cannot be longer than 1,920 characters", the abstract appearing here is slightly shorter than that in the PDF fil

    Construction of an integrated consensus map of the Apple genome based on four mapping populations

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    An integrated consensus genetic map for apple was constructed on the basis of segregation data from four genetically connected crosses (C1¿=¿Discovery × TN10-8, C2¿=¿Fiesta × Discovery, C3¿=¿Discovery × Prima, C4¿=¿Durello di Forli × Fiesta) with a total of 676 individuals using CarthaGene® software. First, integrated female¿male maps were built for each population using common female¿male simple sequence repeat markers (SSRs). Then, common SSRs over populations were used for the consensus map integration. The integrated consensus map consists of 1,046 markers, of which 159 are SSR markers, distributed over 17 linkage groups reflecting the basic chromosome number of apple. The total length of the integrated consensus map was 1,032 cM with a mean distance between adjacent loci of 1.1 cM. Markers were proportionally distributed over the 17 linkage groups (¿ 2¿=¿16.53, df¿=¿16, p¿=¿0.41). A non-uniform marker distribution was observed within all of the linkage groups (LGs). Clustering of markers at the same position (within a 1-cM window) was observed throughout LGs and consisted predominantly of only two to three linked markers. The four integrated female¿male maps showed a very good colinearity in marker order for their common markers, except for only two (CH01h01, CH05g03) and three (CH05a02z, NZ02b01, Lap-1) markers on LG17 and LG15, respectively. This integrated consensus map provides a framework for performing quantitative trait locus (QTL) detection in a multi-population design and evaluating the genetic background effect on QTL expression

    A comparison of SNPs and microsatellites as linkage mapping markers: lessons from the zebra finch (Taeniopygia guttata)

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    Background: Genetic linkage maps are essential tools when searching for quantitative trait loci (QTL). To maximize genome coverage and provide an evenly spaced marker distribution a combination of different types of genetic marker are sometimes used. In this study we created linkage maps of four zebra finch (Taeniopygia guttata) chromosomes (1, 1A, 2 and 9) using two types of marker, Single Nucleotide Polymorphisms (SNPs) and microsatellites. To assess the effectiveness and accuracy of each kind of marker we compared maps built with each marker type separately and with both types of marker combined. Linkage map marker order was validated by making comparisons to the assembled zebra finch genome sequence. Results: We showed that marker order was less reliable and linkage map lengths were inflated for microsatellite maps relative to SNP maps, apparently due to differing error rates between the two types of marker. Guidelines on how to minimise the effects of error are provided. In particular, we show that when combining both types of marker the conventional process of building linkage maps, whereby the most informative markers are added to the map first, has to be modified in order to improve map accuracy. Conclusions: When using multiple types and large numbers of markers to create dense linkage maps, the least error prone loci (SNPs) rather than the most informative should be used to create framework maps before the addition of other potentially more error prone markers (microsatellites). This raises questions about the accuracy of marker order and predicted recombination rates in previous microsatellite linkage maps which were created using the conventional building process, however, provided suitable error detection strategies are followed microsatellite-based maps can continue to be regarded as reasonably reliable

    Restriction Fragment Length Polymorphism Linkage Map for Arabidopsis thaliana

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    We have constructed a restriction fragment length polymorphism linkage map for the nuclear genome of the flowering plant Arabidopsis thaliana. The map, containing 90 randomly distributed molecular markers, is physically very dense; >50% of the genome is within 1.9 centimorgans, or approx 270 kilobase pairs, of the mapped DNA fragments. The map was based on the meiotic segregation of markers in two different crosses. The restriction fragment length polymorphism linkage groups were integrated with the five classically mapped linkage groups by virtue of mapped mutations included in these crosses. Markers consist of both cloned Arabidopsis genes and random low-copy-number genomic DNA clones that are able to detect polymorphisms with the restriction enzymes EcoRI, Bgl II, and/or Xba I. These cloned markers can serve as starting points for chromosome walking, allowing for the isolation of Arabidopsis genes of known map location. The restriction fragment length polymorphism map also can associate clones of unknown gene function with mutant phenotypes, and vice versa

    Joint assembly and genetic mapping of the Atlantic horseshoe crab genome reveals ancient whole genome duplication

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    Horseshoe crabs are marine arthropods with a fossil record extending back approximately 450 million years. They exhibit remarkable morphological stability over their long evolutionary history, retaining a number of ancestral arthropod traits, and are often cited as examples of "living fossils." As arthropods, they belong to the Ecdysozoa}, an ancient super-phylum whose sequenced genomes (including insects and nematodes) have thus far shown more divergence from the ancestral pattern of eumetazoan genome organization than cnidarians, deuterostomes, and lophotrochozoans. However, much of ecdysozoan diversity remains unrepresented in comparative genomic analyses. Here we use a new strategy of combined de novo assembly and genetic mapping to examine the chromosome-scale genome organization of the Atlantic horseshoe crab Limulus polyphemus. We constructed a genetic linkage map of this 2.7 Gbp genome by sequencing the nuclear DNA of 34 wild-collected, full-sibling embryos and their parents at a mean redundancy of 1.1x per sample. The map includes 84,307 sequence markers and 5,775 candidate conserved protein coding genes. Comparison to other metazoan genomes shows that the L. polyphemus genome preserves ancestral bilaterian linkage groups, and that a common ancestor of modern horseshoe crabs underwent one or more ancient whole genome duplications (WGDs) ~ 300 MYA, followed by extensive chromosome fusion

    An Ultra-High-Density, Transcript-Based, Genetic Map of Lettuce.

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    We have generated an ultra-high-density genetic map for lettuce, an economically important member of the Compositae, consisting of 12,842 unigenes (13,943 markers) mapped in 3696 genetic bins distributed over nine chromosomal linkage groups. Genomic DNA was hybridized to a custom Affymetrix oligonucleotide array containing 6.4 million features representing 35,628 unigenes of Lactuca spp. Segregation of single-position polymorphisms was analyzed using 213 F7:8 recombinant inbred lines that had been generated by crossing cultivated Lactuca sativa cv. Salinas and L. serriola acc. US96UC23, the wild progenitor species of L. sativa The high level of replication of each allele in the recombinant inbred lines was exploited to identify single-position polymorphisms that were assigned to parental haplotypes. Marker information has been made available using GBrowse to facilitate access to the map. This map has been anchored to the previously published integrated map of lettuce providing candidate genes for multiple phenotypes. The high density of markers achieved in this ultradense map allowed syntenic studies between lettuce and Vitis vinifera as well as other plant species

    An integrated genomic approach for the study of mandibular prognathism in the European seabass (Dicentrarchus labrax)

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    Skeletal anomalies in farmed fish are a relevant issue affecting animal welfare and health and causing significant economic losses. Here, a high-density genetic map of European seabass for QTL mapping of jaw deformity was constructed and a genome-wide association study (GWAS) was carried out on a total of 298 juveniles, 148 of which belonged to four full-sib families. Out of 298 fish, 107 were affected by mandibular prognathism (MP). Three significant QTLs and two candidate SNPs associated with MP were identified. The two GWAS candidate markers were located on ChrX and Chr17, both in close proximity with the peaks of the two most significant QTLs. Notably, the SNP marker on Chr17 was positioned within the Sobp gene coding region, which plays a pivotal role in craniofacial development. The analysis of differentially expressed genes in jaw-deformed animals highlighted the "nervous system development" as a crucial pathway in MP. In particular, Zic2, a key gene for craniofacial morphogenesis in model species, was significantly down-regulated in MP-affected animals. Gene expression data revealed also a significant down-regulation of Sobp in deformed larvae. Our analyses, integrating transcriptomic and GWA methods, provide evidence for putative mechanisms underlying seabass jaw deformity

    Detection of growth-related QTLs in turbot (Scophtalmus maximux)

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    Background The turbot (Scophthalmus maximus) is a highly appreciated European aquaculture species. Growth related traits constitute the main goal of the ongoing genetic breeding programs of this species. The recent construction of a consensus linkage map in this species has allowed the selection of a panel of 100 homogeneously distributed markers covering the 26 linkage groups (LG) suitable for QTL search. In this study we addressed the detection of QTL with effect on body weight, length and Fulton's condition factor. Results Eight families from two genetic breeding programs comprising 814 individuals were used to search for growth related QTL using the panel of microsatellites available for QTL screening. Two different approaches, maximum likelihood and regression interval mapping, were used in order to search for QTL. Up to eleven significant QTL were detected with both methods in at least one family: four for weight on LGs 5, 14, 15 and 16; five for length on LGs 5, 6, 12, 14 and 15; and two for Fulton's condition factor on LGs 3 and 16. In these LGs an association analysis was performed to ascertain the microsatellite marker with the highest apparent effect on the trait, in order to test the possibility of using them for marker assisted selection. Conclusions The use of regression interval mapping and maximum likelihood methods for QTL detection provided consistent results in many cases, although the high variation observed for traits mean among families made it difficult to evaluate QTL effects. Finer mapping of detected QTL, looking for tightly linked markers to the causative mutation, and comparative genomics are suggested to deepen in the analysis of QTL in turbot so they can be applied in marker assisted selection programs

    Anchoring linkage groups of the Rosa genetic map to physical chromosomes with tyramide-FISH and EST-SNP markers

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    In order to anchor Rosa linkage groups to physical chromosomes, a combination of the Tyramide-FISH technology and the modern molecular marker system based on High Resolution Melting (HRM) is an efficient approach. Although, Tyramide-FISH is a very promising technique for the visualization of short DNA probes, it is very challenging for plant species with small chromosomes such as Rosa. In this study, we successfully applied the Tyramide-FISH technique for Rosa and compared different detection systems. An indirect detection system exploiting biotinylated tyramides was shown to be the most suitable technique for reliable signal detection. Three gene fragments with a size of 1100 pb-1700 bp (Phenylalanine Ammonia Lyase, Pyrroline-5-Carboxylate Synthase and Orcinol O-Methyl Transferase) have been physically mapped on chromosomes 7, 4 and 1, respectively, of Rosa wichurana. The signal frequency was between 25% and 40%. HRM markers of these 3 gene fragments were used to include the gene fragments on the existing genetic linkage map of Rosa wichurana. As a result, three linkage groups could be anchored to their physical chromosomes. The information was used to check for synteny between the Rosa chromosomes and Fragaria
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