Comparison of mixed-model approaches for association mapping in rapeseed, potato, sugar beet, maize, and Arabidopsis

<p>Abstract</p> <p>Background</p> <p>In recent years, several attempts have been made in plant genetics to detect QTL by using association mapping methods. The objectives of this study were to (i) evaluate various methods for association mapping in five plant species and (ii) for three traits in each of the plant species compare the <it>T</it>_<it>opt</it>, the restricted maximum likelihood (REML) estimate of the conditional probability that two genotypes carry at the same locus alleles that are identical in state but not identical by descent. In order to compare the association mapping methods based on scenarios with realistic estimates of population structure and familial relatedness, we analyzed phenotypic and genotypic data of rapeseed, potato, sugar beet, maize, and Arabidopsis. For the same reason, QTL effects were simulated on top of the observed phenotypic values when examining the adjusted power for QTL detection.</p> <p>Results</p> <p>The correlation between the <it>T</it>_{<it>opt </it>}values identified using REML deviance profiles and profiles of the mean of squared difference between observed and expected <it>P </it>values was 0.83.</p> <p>Conclusion</p> <p>The mixed-model association mapping approaches using a kinship matrix, which was based on <it>T</it>_<it>opt</it>, were more appropriate for association mapping than the recently proposed QK method with respect to the adherence to the nominal <it>α </it>level and the adjusted power for QTL detection. Furthermore, we showed that <it>T</it>_{<it>opt </it>}differs considerably among the five plant species but only marginally among different traits.</p

Linkage disequilibrium and association mapping in elite germplasm of European maize

In der Pflanzengenetik ist die Kopplungsanalyse das Standardwerkzeug um Genloci zu identifizieren, die für quantitative Merkmale kodieren (QTL). Ein alternativer und vielversprechender Ansatz, der in der Humangenetik bereits erfolgreich dazu eingesetzt wurde, um QTL für Mukoviszidose und Alzheimer-Krankheit aufzufinden, ist die Assoziationskartierung. In der vorliegenden Arbeit werden die Anwendbarkeit von Assoziationskartierungsmethoden zum Auffinden von QTL in Maiselitezüchtungsmaterial untersucht sowie für diesen Zweck geeignete biometrische Methoden entwickelt. Ob Assoziationskartierungsansätze auch in Pflanzenzüchtungspopulationen zum Auffinden von QTL eingesetzt werden können, hängt vom Ausmaß des Gametenphasenungleichgewichtes (GPU) in der interessierenden Population ab. Des weiteren wird die Anwendbarkeit von Assoziationskartierungsmethoden von den Kräften beeinflußt, die in der betreffenden Population GPU verursachen und aufrechterhalten. Die Ziele unserer Studien waren (i) die Erfassung des Ausmaßes und der genomweiten Verteilung des GPU zwischen Mikrosatelliten (SSR) Markern, (ii) der Vergleich dieser Ergebnisse mit denjenigen für Amplifizierte-Fragment-Längen-Polymorphismus (AFLP) Markern sowie (iii) die Untersuchung von Kraften, die in Maiselitezüchtungsmaterial GPU verursachen und aufrechterhalten. Unsere Studien basierten sowohl auf experimentellen Daten von europäischen Maiseliteinzuchtlinien als auch auf Computersimulationen. Unsere Ergebnisse legen nahe, dass in europäischem Maiselitezüchtungsmaterial das Ausmaß an GPU sowohl zwischen SSR Markern als auch zwischen AFLP Markern ausreichend ist, um mit Hilfe der Assoziationskartierung genomweit QTL auffinden zu können. Da die Güte von SSR Markern GPU aufzufinden höher ist als diejenige von AFLP Markern, sind in Populationen mit kurzer Rekombinationsgeschichte SSR Marker geeigneter für Assoziationskartierungen als AFLP Marker. In Populationen mit langer Rekombinationsgeschichte, für die kein signifikantes GPU zwischen SSR Markern zu erwarten ist, sind AFLP Marker geeigneter für Assoziationskartierungen, da in diesem Fall ihre mit gleichem finanziellem Aufwand erzeugte höhere Markerdichte genutzt werden kann. Die Ergebnisse unserer experimentellen Untersuchungen und Simulationsstudien deuten darauf hin, dass in Pflanzenzüchtungspopulationen nicht nur physikalische Kopplung eine Ursache für GPU ist, sondern auch Verwandschaft, Populationsstratifizierung, genetische Drift und Selektion. Der Assoziationstest, der bislang in der Pflanzengenetik eingesetzt wurde, ist der ?logistic regression ratio test? (LRRT). Dieser Test korrigiert allerdings nur für GPU, das durch Populationsstratifizierung verursacht wird. Aus diesem Grund wird erwartet, dass der LRRT das alpha-Niveau nicht einhält, wenn er zur Assoziationskartierung in Populationen eingesetzt wird, in denen GPU vorhanden ist, das durch Verwandschaft, genetische Drift oder Selektion verursacht wird. Die Ziele unserer Studie waren (i) den ?quantitative pedigree disequilibrium test? so zu modifizieren, dass er zur Assoziationskartierung in Pflanzenzüchtungspopulationen eingesetzt werden kann und (ii) den neuentwickelten Test (QIPDT) hinsichtlich seiner Güte und Typ I Fehlerrate bei der Detektion von QTL zu untersuchen und mit dem bislang eingesetzten LRRT zu vergleichen. Diese Studie basierte auf Computersimulationen. Wir beobachteten für den QIPDT eine höhere Güte, QTL aufzufinden, als für den LRRT, wenn Daten verwendet wurden, die routinemäßig in Pflanzenzüchtungsprogrammen erhoben wurden. Im Gegensatz zum LRRT hielt der QIPDT stets das alpha-Niveau ein. Diese Ergebnisse belegen, dass der QIPDT zur genomweiten Assoziationskartierung mit Daten, die routinemäßig in Pflanzenzüchtungsprogrammen erhoben werden, geeigneter ist als der LRRT. Epistatische Interaktionen zwischen QTL tragen wesentlich zur genetischen Variation komplexer Merkmale bei. Die Ziele unserer Studie waren (i) Populationen rekombinanter Inzuchtlinien (RIL), die von einem geschachtelten Kreuzungsschema abgeleitet wurden, hinsichtlich ihrer Güte und Rate an falsch Positiven beim Auffinden epistatischer Interaktionen zwischen drei Loci, zu untersuchen und (ii) diese Ergebnisse mit jenen zu vergleichen, die beobachtet werden, wenn RIL von vollständigen oder unvollständigen Kreuzungsdiallelen abgeleitet wurden. Die Computersimulationen dieser Studie basierten auf Haplotypdaten von 26 Maisinzuchtlinien. Sowohl die Güte als auch die Rate an falsch Positiven beim Auffinden von epistatischen Interaktionen zwischen drei Loci waren für 5000 RIL, die von einem geschachtelten Kreuzungsschema abgeleitet wurden, auf einem Niveau, das vielversprechend für deren Detektion ist. Für RIL, die von optimal allozierten distanz-basierten Kreuzungsschemata abgeleitet wurden, wurde eine höhere Güte, epistatische Interaktionen zwischen drei Loci aufzufinden, beobachtet, als für die gleiche Anzahl an RIL, die von einem geschachtelten Kreuzungsschema oder Kreuzungsdiallelen abgeleitet wurden. Unsere Ergebnisse belegen, dass Assoziationskartierungsmethoden, die an die Besonderheiten von Pflanzenzüchtungspopulationen angepasst sind, in diesen erfolgreich zum Auffinden von QTL eingesetzt werden können.Linkage mapping has become a routine tool for the identification of quantitative trait loci (QTL) in plants. An alternative, promising approach is association mapping, which has been successfully applied in human genetics to detect QTL coding for diseases. The objectives of this research were to examine the feasibility of association mapping in elite maize breeding populations and develop for this purpose appropriate biometric methods. The feasibility of association mapping depends on the extent of linkage disequilibrium (LD) as well as on the forces generating and conserving LD in the population under consideration. The objectives of our studies were to (i) examine the extent and genomic distribution of LD between pairs of simple sequence repeat (SSR) marker loci, (ii) compare these results with those obtained with amplified fragment length polymorphism (AFLP) markers, and (iii) investigate the forces generating and conserving LD in plant breeding populations. Our studies were based on experimental data of European elite maize inbreds as well as on computer simulations modeling the breeding history of the European flint heterotic group. The experimental results on European elite maize germplasm suggested that the extent of LD between SSR markers as well as AFLP markers are encouraging for the detection of marker-phenotype associations in genomewide scans. In populations with a short history of recombination, SSRs are advantageous over AFLPs in that they have a higher power to detect LD. In contrast, in populations with a long history of recombination, for which no LD is expected between pairs of SSR markers, AFLP markers should be favored over SSRs because then their higher marker density that is generated with a fixed budget can be used. Furthermore, the results of our experimental and simulation studies indicated that not only physical linkage is a cause of LD in plant breeding populations, but also relatedness, population stratification, genetic drift, and selection. So far, in plant genetics the logistic regression ratio test (LRRT) has been applied as a population-based association mapping approach. However, this test does only correct for LD caused by population stratification. The objectives of the presented study were to (i) adapt the quantitative pedigree disequilibrium test to typical pedigrees of inbred lines produced in plant breeding programs and (ii) compare the newly developed quantitative inbred pedigree disequilibrium test (QIPDT) and the commonly employed LRRT with respect to the power and type I error rate of QTL detection. This study was based on computer simulations modeling the breeding history of the European maize heterotic groups. In QIPDT the power of QTL detection was higher with 75 extended pedigrees than in LRRT with 75 independent inbreds. Furthermore, while the type I error rate of LRRT surpassed the nominal ® level, the QIPDT adhered to it. These results suggested that the QIPDT is superior to the LRRT for genome-wide association mapping if data collected routinely in plant breeding programs are available. Epistatic interactions among QTL contribute substantially to the genetic variation in complex traits. The main objectives of our study were to (i) investigate by computer simulations the power and proportion of false positives for detecting three-way interactions among QTL involved in a metabolic pathway in populations of recombinant inbred lines (RILs) derived from a nested design and (ii) compare these estimates to those obtained for detecting three-way interactions among QTL in RIL populations derived from diallel and different partial diallel mating designs. The computer simulations of this study were based on single nucleotide polymorphism haplotype data of 26 diverse maize inbreds. The power and proportion of false positives to detect three-way interactions with 5000 RILs derived from a nested design was relatively high for both the 4 QTL and the 12 QTL scenario. Higher power to detect three-way interactions was observed for RILs derived from optimally allocated distancebased designs than for RILs derived from a nested or diallel design. Our results suggested that association mapping methods adapted to the special features of plant breeding populations have the potential to overcome the limitations of classical linkage mapping methods

Genome-wide distribution of genetic diversity and linkage disequilibrium in elite sugar beet germplasm

<p>Abstract</p> <p>Background</p> <p>Characterization of population structure and genetic diversity of germplasm is essential for the efficient organization and utilization of breeding material. The objectives of this study were to (i) explore the patterns of population structure in the pollen parent heterotic pool using different methods, (ii) investigate the genome-wide distribution of genetic diversity, and (iii) assess the extent and genome-wide distribution of linkage disequilibrium (LD) in elite sugar beet germplasm.</p> <p>Results</p> <p>A total of 264 and 238 inbred lines from the yield type and sugar type inbreds of the pollen parent heterotic gene pools, respectively, which had been genotyped with 328 SNP markers, were used in this study. Two distinct subgroups were detected based on different statistical methods within the elite sugar beet germplasm set, which was in accordance with its breeding history. MCLUST based on principal components, principal coordinates, or lapvectors had high correspondence with the germplasm type information as well as the assignment by STRUCTURE, which indicated that these methods might be alternatives to STRUCTURE for population structure analysis. Gene diversity and modified Roger's distance between the examined germplasm types varied considerably across the genome, which might be due to artificial selection. This observation indicates that population genetic approaches could be used to identify candidate genes for the traits under selection. Due to the fact that <it>r</it>²<it>></it>0.8 is required to detect marker-phenotype association explaining less than 1% of the phenotypic variance, our observation of a low proportion of SNP loci pairs showing such levels of LD suggests that the number of markers has to be dramatically increased for powerful genome-wide association mapping.</p> <p>Conclusions</p> <p>We provided a genome-wide distribution map of genetic diversity and linkage disequilibrium for the elite sugar beet germplasm, which is useful for the application of genome-wide association mapping in sugar beet as well as the efficient organization of germplasm.</p

Ups and downs of a transcriptional landscape shape iron deficiency associated chlorosis of the maize inbreds B73 and Mo17

BACKGROUND: Improving nutrient homeostasis is a major challenge of a sustainable maize cultivation, and cornerstone to ensure food supply for a growing world population. Although, iron constitutes an important nutrient, iron availability is limited. In this respect, iron deficiency associated chlorosis causes severe yield losses every year. Natural variation of the latter trait has yet not been addressed in maize and was therefore studied in the present analysis. RESULTS: In this study, we i) report about the contrasting chlorosis phenotypes of the inbreds B73 and Mo17 at 10 and 300 μM iron regime, ii) identified over 400 significantly regulated transcripts (FDR < 0.05) within both inbreds at these growth conditions by deep RNA-Sequencing, iii) linked the gained knowledge with QTL information about iron deficiency related traits within the maize intermated B73 by Mo17 (IBM) population, and iv) highlighted contributing molecular pathways. In this respect, several genes within methionine salvage pathway and phytosiderophore synthesis were found to present constitutively high expression in Mo17, even under sufficient iron supply. Moreover, the same expression pattern could be observed for two putative bHLH transcription factors. In addition, a number of differentially expressed genes showed a co-localisation with QTL confidence intervals for iron deficiency related traits within the IBM population. CONCLUSIONS: Our study highlights differential iron deficiency associated chlorosis between B73 and Mo17 and represents a valuable resource for differentially expressed genes upon iron limitation and chlorosis response. Besides identifying two putative bHLH transcription factors, we propose that methionine salvage pathway and sterol metabolism amongst others; underlie the contrasting iron deficiency related chlorosis phenotype of both inbreds. Altogether, this study emphasizes a contribution of selected genes and pathways on natural trait variation within the IBM population

Natural variation for BYDV resistance in maize

With increasing winter temperatures, Barley yellow dwarf virus (BYDV) is expected to become a prominent problem also in maize cultivation. Breeding for resistance is the best alternative to control the disease and break the transmission cycle of the virus. The objectives of our study were to (I) determine phenotypic and genotypic variation in five segregating populations of maize with respect to BYDV tolerance or resistance as well as (II) quantify the influence of BYDV infection on plant performance traits. In 2011, five segregating populations with a total of 445 genotypes were grown at two locations in Germany. Plants were inoculated with BYDV-PAV transmitted by aphids of the species Rhopalosiphum padi. We observed considerable genotypic variance for the traits virus concentration as measured by double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) as well as expression of symptoms. Furthermore, heritabilities were high for the plant performance traits ear height and plant height. Correlation coefficients between all pairs of traits were significantly different from 0 (P < 0.05). Genotypes of the inoculated variant were reduced in plant height by 3 cm, ear height by 6 cm, and flowered 3 days earlier compared to genotypes of the non-inoculated variant. The results of our study suggested a high potential for breeding of BVDY resistant / tolerant maize

Linkage mapping of Barley yellow dwarf virus resistance in connected populations of maize

BACKGROUND: With increasing winter temperatures, Barley yellow dwarf virus (BYDV) is expected to become an increasing problem in maize cultivation in Germany. Earlier studies revealed that BYDV has a negative impact on maize performance. Molecular markers would accelerate the development of BYDV resistant maize. Therefore, the objectives of this study were (i) the identification of quantitative trait loci (QTL) for BYDV resistance in five connected segregating maize populations in a field experiment and (ii) their comparison with the QTL detected under greenhouse conditions. RESULTS: In linkage analyses of the traits virus extinction, infection rate, and the symptom red edges, a highly associated major QTL was identified on chromosome 10. This QTL explained 45% of the phenotypic variance for the traits virus extinction and infection rate and 30% for the symptom red edges. CONCLUSION: We could show that BYDV resistance traits are oligogenically inherited. The QTL on chromosome 10 could be observed in the connected linkage analyses and in the single population analyses. Furthermore, this QTL could also be confirmed in the greenhouse experiment. Our results let suggest that this QTL is involved in multiple virus resistance and the markers are promising for marker assisted selection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12870-015-0420-x) contains supplementary material, which is available to authorized users

Transient spurious intrathecal immunoglobulin synthesis in neurological patients after therapeutic apheresis

Background The analysis of cerebrospinal fluid (CSF) is usually done under steady-state conditions, when proteins (e.g., immunoglobulins) reach diffusion equilibrium between blood and CSF. However, little data has been published on CSF analysis under non-steady-state conditions after therapeutic apheresis. By reducing serum proteins (e.g., immunoglobulins), while leaving CSF unchanged, therapeutic apheresis might cause spuriously altered intrathecal immunoglobulin fractions. Methods Based on the incidental finding of plasma exchange-induced increased intrathecal immunoglobulin fractions in a cohort of 12 unsystematically selected patients with various neurological disorders, we retrospectively investigated CSF results that had been raised during routine diagnostic work-up from 41 consecutive neurological patients (predominantly Guillain-Barré syndrome and autoimmune encephalitis) treated with plasmapheresis or immunoadsorption in a tertiary care university hospital in whom lumbar puncture (LP) was performed after a varying number of treatments of therapeutic apheresis. Results Only when LP was performed 1 day after therapeutic apheresis, spurious quantitative intrathecal immunoglobulin (Ig) synthesis of at least one subclass (IgG, IgA and/or IgM) was found in 68.4 % of the patients, irrespective of the number of treatments, in all age groups and independent of other previous immunotherapies (e.g., steroids). This phenomenon occurred only transiently and was almost always accompanied by an elevation of the IgG index. In one patient, an elevated IgG index was noticed even 2 days after plasmapheresis. Neither quantitative Ig synthesis, nor elevated IgG index was observed when the LP was performed three or more days after therapeutic apheresis. Conclusions Spurious quantitative intrathecal Ig synthesis and increased IgG index are common findings shortly after plasmapheresis or immunoadsorption due to altered serum immunoglobulin levels. Knowledge of this phenomenon is needed for clinicians to prevent false interpretations leading to unnecessary diagnostic and therapeutic procedures. Misdiagnoses can be avoided by considering the characteristic CSF constellation including absence of oligoclonal bands and the close temporal relation to therapeutic apheresi

Approach For Data-Based Optimization In Cell Finishing of Battery Production

Due to the global warming, a significant reduction in the emission of greenhouse gases is necessary. One part of the solution is the electrification of today's transportation and traffic sector. An essential component of today's electric vehicles is the lithium-ion battery (LIB), which is largely responsible for their range, performance and cost. In order to increase the use of such climate-friendly technologies, it is therefore essential to reduce the production costs of LIBs. With a duration of up to three weeks, the process steps of formation and aging are particularly capital-intensive and have high demands on storage capacities. Formation and aging therefore account for up to 30% of the manufacturing costs for battery cells. During formation, the solid electrolyte interphase (SEI) is formed, which has a major influence on the quality and lifetime of the LIB, among other things. In order to reduce production costs and simultaneously increase battery cell quality, it is therefore necessary to optimize the formation and aging process. Because of the complexity and the interdependency of these processes towards previous process parameters the application of machine learning algorithm is predestined to optimize these process steps. For this purpose, a general approach for the application of a machine learning algorithm in the formation and aging are first analysed and relevant parameters from the literature as well as reasonable assumptions about the structure are derived. Based on these requirements and boundary conditions a machine learning algorithm structure will be developed to optimize the cell finishing process in the battery cell production

Connection between the Jurassic oceanic lithosphere of the Gulf of Cádiz and the Alboran slab imaged by Sp receiver functions

We investigate the lithospheric structure beneath the Gibraltar arc (western Mediterranean) using S-wave receiver functions (SRFs). From a dense network deployed in the Ibero-Maghrebian region during different seismic surveys, we calculated ~11,000 SRFs that sample the upper mantle detecting the lithosphere-asthenosphere boundary (LAB). The observed seismic LAB belongs to different lithospheric domains: Iberian and African forelands, Alboran domain, and Atlantic Ocean. Common conversion point (CCP) migrated profiles show the geometrical relation among them. Under the Strait of Gibraltar, we observe a deep LAB (~150 km). It can be associated with Jurassic-age lithosphere of ~120 km thickness, one of the thickest ever reported in oceanic environments. There is an abrupt offset between the oceanic LAB and the shallow (80-km-deep) continental LAB of the Iberian foreland, suggesting displacement along a former transform fault. The northwestern African continental LAB is 90–100 km deep. The oceanic LAB under the Gibraltar arc continues to ~180 km depth beneath the Alboran Sea, showing the connection between the Alboran slab and the oceanic lithosphere in the central Gulf of Cádiz. This geometry agrees with an ~200-km-wide corridor of oceanic lithosphere between the central Atlantic and the Alpine Tethys, developed during the Middle–Late Jurassic. Our results support the proposed westward rollback of an oceanic east-dipping slab, which has continuity at least to the central Gulf of Cádiz.This work was supported by the Spanish national projects CGL2015-67130-C2-2-R/FEDER and CGL2012-31472