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Y I Ronin

Publications and source records attributed to Y I Ronin.

13 recordsLinked to original sources

Multilocus consensus genetic maps (MCGM): formulation, algorithms, and results.

In process of creating genetic maps different labs/research groups obtain overlapping parts of the map. Merging these parts into one integrative map is based on looking for maximum shared marker orders among the maps. Really, not all shared markers of such maps have consensus order that obstructs building of the integrative maps. In this paper we propose a new approach to build verified multilocus consensus genetic maps in which shared markers always are integrated in stable consensus order. The approach is based on combined analysis of initial mapping data rather than manipulating with previously constructed maps. We show that more effective and reliable solutions may be obtained based on "synchronized ordering" facilitated by cycles of "re-sampling-->ordering-->removing unstable markers". The proposed formulation of consensus genetic mapping can be considered as a version of traveling salesperson problem (TSP) that we refer to as synchronized-TSP. From the viewpoint of optimization, synchronized-TSP belongs to discrete constrained optimization problems. Earlier we developed new powerful and fast guided evolution strategy algorithms for some types of discrete constrained optimization. These algorithms were used here as a basis for solving more challenging problems of consensual marker ordering.

Algorithms↗

Fast and high precision algorithms for optimization in large-scale genomic problems.

There are several very difficult problems related to genetic or genomic analysis that belong to the field of discrete optimization in a set of all possible orders. With n elements (points, markers, clones, sequences, etc.), the number of all possible orders is n!/2 and only one of these is considered to be the true order. A classical formulation of a similar mathematical problem is the well-known traveling salesperson problem model (TSP). Genetic analogues of this problem include: ordering in multilocus genetic mapping, evolutionary tree reconstruction, building physical maps (contig assembling for overlapping clones and radiation hybrid mapping), and others. A novel, fast and reliable hybrid algorithm based on evolution strategy and guided local search discrete optimization was developed for TSP formulation of the multilocus mapping problems. High performance and high precision of the employed algorithm named guided evolution strategy (GES) allows verification of the obtained multilocus orders based on different computing-intensive approaches (e.g., bootstrap or jackknife) for detection and removing unreliable marker loci, hence, stabilizing the resulting paths. The efficiency of the proposed algorithm is demonstrated on standard TSP problems and on simulated data of multilocus genetic maps up to 1000 points per linkage group.

Algorithms↗

Efficient multipoint mapping: making use of dominant repulsion-phase markers.

The paper is devoted to the problem of multipoint gene ordering with a particular focus on "dominance" complication that acts differently in conditions of coupling-phase and repulsion-phase markers. To solve the problem we split the dataset into two complementary subsets each containing shared codominant markers and dominant markers in the coupling-phase only. Multilocus ordering in the proposed algorithm is based on pairwise recombination frequencies and using the well-known travelling salesman problem (TSP) formalization. To obtain accurate results, we developed a multiphase algorithm that includes synchronized-marker ordering of two subsets assisted by re-sampling-based map verification, combining the resulting maps into an integrated map followed by verification of the integrated map. A new synchronized Evolution-Strategy discrete optimization algorithm was developed here for the proposed multilocus ordering approach in which common codominant markers facilitate stabilization of the marker order of the two complementary maps. High performance of the employed algorithm allows systematic treatment for the problem of verification of the obtained multilocus orders, based on computing-intensive bootstrap and jackknife technologies for detection and removing unreliable marker scores. The efficiency of the proposed algorithm was demonstrated on simulated and real data.

Algorithms↗

Enhanced efficiency of quantitative trait loci mapping analysis based on multivariate complexes of quantitative traits.

An approach to increase the efficiency of mapping quantitative trait loci (QTL) was proposed earlier by the authors on the basis of bivariate analysis of correlated traits. The power of QTL detection using the log-likelihood ratio (LOD scores) grows proportionally to the broad sense heritability. We found that this relationship holds also for correlated traits, so that an increased bivariate heritability implicates a higher LOD score, higher detection power, and better mapping resolution. However, the increased number of parameters to be estimated complicates the application of this approach when a large number of traits are considered simultaneously. Here we present a multivariate generalization of our previous two-trait QTL analysis. The proposed multivariate analogue of QTL contribution to the broad-sense heritability based on interval-specific calculation of eigenvalues and eigenvectors of the residual covariance matrix allows prediction of the expected QTL detection power and mapping resolution for any subset of the initial multivariate trait complex. Permutation technique allows chromosome-wise testing of significance for the whole trait complex and the significance of the contribution of individual traits owing to: (a) their correlation with other traits, (b) dependence on the chromosome in question, and (c) both a and b. An example of application of the proposed method on a real data set of 11 traits from an experiment performed on an F(2)/F(3) mapping population of tetraploid wheat (Triticum durum x T. dicoccoides) is provided.

Chromosome Mapping↗

Molecular genetic maps in wild emmer wheat, Triticum dicoccoides: genome-wide coverage, massive negative interference, and putative quasi-linkage.

The main objectives of the study reported here were to construct a molecular map of wild emmer wheat, Triticum dicoccoides, to characterize the marker-related anatomy of the genome, and to evaluate segregation and recombination patterns upon crossing T. dicoccoides with its domesticated descendant Triticum durum (cultivar Langdon). The total map length exceeded 3000 cM and possibly covered the entire tetraploid genome (AABB). Clusters of molecular markers were observed on most of the 14 chromosomes. AFLP (amplified fragment length polymorphism) markers manifested a random distribution among homologous groups, but not among genomes and chromosomes. Genetic differentiation between T. dicoccoides and T. durum was attributed mainly to the B genome as revealed by AFLP markers. The segregation-distorted markers were mainly clustered on 4A, 5A, and 5B chromosomes. Homeoalleles, differentially conferring the vigor of gametes, might be responsible for the distortion on 5A and 5B chromosomes. Quasilinkage, deviation from free recombination between markers of nonhomologous chromosomes, was discovered. Massive negative interference was observed in most of the chromosomes (an excess of double crossovers in adjacent intervals relative to the expected rates on the assumption of no interference). The general pattern of distribution of islands of negative interference included near-centromeric location, spanning the centromere, and median/subterminal location. [An appendix describing the molecular marker loci is available as an online supplement at http://www.genome.org.]

Binomial Distribution↗

Single- and multiple-trait mapping analysis of linked quantitative trait loci. Some asymptotic analytical approximations.

Estimating the resolution power of mapping analysis of linked quantitative trait loci (QTL) remains a difficult problem, which has been previously addressed mainly by Monte Carlo simulations. The analytical method of evaluation of the expected LOD developed in this article spreads the "deterministic sampling" approach for the case of two linked QTL for single- and two-trait analysis. Several complicated questions are addressed through this evaluation: the dependence of QTL detection power on the QTL effects, residual correlation between the traits, and the effect of epistatic interaction between the QTL for one or both traits on expected LOD (ELOD), etc. Although this method gives only an asymptotic estimation of ELOD, it allows one to get an approximate assessment of a broad spectrum of mapping situations. A good correspondence was found between the ELODs predicted by the model and LOD values averaged over Monte Carlo simulations.

Chromosome Mapping↗

Isolation of microsatellite and RAPD markers flanking the Yr15 gene of wheat using NILs and bulked segregant analysis.

Microsatellite and random amplified polymorphic DNA (RAPD) primers were used to identify molecular markers linked to the Yr15 gene which confer resistance to stripe rust (Puccina striiformis Westend) in wheat. By using near isogenic lines (NILs) for the Yr15 gene and a F2 mapping population derived from crosses of these lines and phenotyped for resistance, we identified one microsatellite marker (GWM33) and one RAPD marker (OPA19(800)) linked to Yr15. Then, bulked segregant analysis was used in addition to the NILs to identify RAPD markers linked to the target gene. Using this approach, two RAPD markers linked to Yr15 were identified, one in coupling (UBC199(700)) and one in repulsion phase (UBC212(1200)). After MAPMAKER linkage analysis on the F2 population, the two closest markers were shown to be linked to Yr15 within a distance of about 12 cM. The recombination rates were recalculated using the maximum likelihood technique to take into account putative escaped individuals from the stripe rust resistance test and obtain unbiased distance estimates. As a result of this study, the stripe rust resistance gene Yr15 is surrounded by two flanking PCR markers, UBC199(700) and GWM33, at about 5 cM from each side.

Chromosome Mapping↗

Approximate analysis of QTL-environment interaction with no limits on the number of environments.

An approach is presented here for quantitative trait loci (QTL) mapping analysis that allows for QTL x environment (E) interaction across multiple environments, without necessarily increasing the number of parameters. The main distinction of the proposed model is in the chosen way of approximation of the dependence of putative QTL effects on environmental states. We hypothesize that environmental dependence of a putative QTL effect can be represented as a function of environmental mean value of the trait. Such a description can be applied to take into account the effects of any cosegregating QTLs from other genomic regions that also may vary across environments. The conducted Monte-Carlo simulations and the example of barley multiple environments experiment demonstrate a high potential of the proposed approach for analyzing QTL x E interaction, although the results are only approximated by definition. However, this drawback is compensated by the possibility to utilize information from a potentially unlimited number of environments with a remarkable reduction in the number of parameters, as compared to previously proposed mapping models with QTL x E interactions.

Chromosome Mapping↗

Linkage between quantitative trait loci and marker loci: resolution power of three statistical approaches in single marker analysis.

This paper presents a comparison of three methods of parameter estimation in analysis of linkage between a quantitative trait locus (QTL) and a marker locus: maximum likelihood, mean square for trait cumulative distribution function, and method of moments, employing simulated backcross data. The sensitivity of estimates to violation of assumptions of normality and equal variances were also studied. Some measures of discrepancy between the trait distributions in the QTL groups are considered to evaluate the potential dependence of the resolution capacity of the QTL substitution effect with respect to trait mean value and variance.

Algorithms↗

Sequential estimation of linkage between PCR-generated markers and a target gene employing stepwise bulked analysis.

PCR-based markers are used for targeting plant genes. However, mapping these markers requires laborious and expensive analysis of individual genotypes. We propose here a sequential procedure for fine mapping of PCR markers relative to a target gene. Stepwise bulked analysis is employed to get a censored estimation of the recombination rate. The sequential estimation is compared to fixed sample size design. In both cases, the proposed procedure can achieve a substantial reduction in the number of PCR runs (up to 90-97% for close linkage) as compared to the standard individual-by-individual analysis.

Biometry↗

Genetic supercycles caused by cyclical selection.

Typical behavior of a two-locus genetic system experiencing cyclical selection, includes fixation (in one or both loci) or a stable polymorphic cycle with a period equal to that of environmental changes. By considering the time scale in terms of environmental periods, the last case could be trivially classified as a polymorphic stable point. Here we report on some results showing the complex limiting behavior of diploid population trajectories resulting from selection in a cyclically changing environment. We found that simple cyclical selection could produce genetic supercycles composed of many hundreds of environmental periods.

Alleles↗

Interval mapping of quantitative trait loci employing correlated trait complexes.

An approach to increase the resolution power of interval mapping of quantitative trait (QT) loci is proposed, based on analysis of correlated trait complexes. For a given set of QTs, the broad sense heritability attributed to a QT locus (QTL) (say, A/a) is an increasing function of the number of traits. Thus, for some traits x and y, H(xy)2(A/a) > or = H(x)2(A/a). The last inequality holds even if y does not depend on A/a at all, but x and y are correlated within the groups AA, Aa and aa due to nongenetic factors and segregation of genes from other chromosomes. A simple relationship connects H2 (both in single trait and two-trait analysis) with the expected LOD value, ELOD = -1/2N log(1-H2). Thus, situations could exist that from the inequality H(xy)2(A/a) > or = H(x)2(A/a) a higher resolution is provided by the two-trait analysis as compared to the single-trait analysis, in spite of the increased number of parameters. Employing LOD-score procedure to simulated backcross data, we showed that the resolution power of the QTL mapping model can be elevated if correlation between QTs is taken into account. The method allows us to test numerous biologically important hypotheses concerning manifold effects of genomic segments on the defined trait complex (means, variances and correlations).

Analysis of Variance↗

Cyclical behavior of genotype frequencies in a two-locus population under fluctuating haploid selection.

Numerical iterations have shown that periodic haploid two-locus selection with nonoverlapping generations can produce large-scale cyclical behavior with a period differing significantly from the environmental period. Among other types, we observed slowly damping oscillations with very long periods, stable T-cycles with a length containing several environmental periods, and chaotic-like dynamics. Possible biological implications are discussed.

Environment↗