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At least 343 records · Page 19Linked to original sources
PubMed2002

An AFLP and RFLP linkage map and quantitative trait locus (QTL) analysis of growth traits in Salix.

A genetic linkage map of Salix (2n = 38), composed of 325 AFLP and 38 RFLP markers has been constructed. The map was based on a population ( n = 87) derived from a cross between the male hybrid clone "Björn" ( Salix viminalis x Salix schwerinii) and the female clone "78183" ( S. viminalis). Three hundred fifty seven AFLPs corresponding to DNA polymorphisms heterozygous in one parent and null in the other were scored. A total of 87 RFLP probes, most (83) derived from the Populus genome, yielded 39 and 11 polymorphic loci segregating in a 1:1 and 1:2:1 ratio respectively. Two maps, one for each parent, were constructed according to the "two-way pseudo-testcross" mapping strategy. The S. viminalis x S. schwerinii map (2,404 cM) included 217 markers and formed 26 major linkage groups while S. viminalis (1,844 cM) consisted of 146 markers placed on 18 major groups. In addition, eight and 14 additional minor linkage groups composed of less than four markers (doubles and triplets) were obtained in the S. viminalis x S. schwerinii and the S. viminalis maps, respectively. Both maps provided 70-80% genome coverage with an average density of markers of 14 cM. To investigate possible homologies between the parental maps, 20 AFLPs and 11 RFLPs segregating in 3:1 or 1:2:1 ratios were included in the linkage analysis. Eight linkage groups homologous between the two maps were detected. The present genetic map was used to identify quantitative trait loci (QTLs) affecting growth-related traits. Eleven QTLs were identified; seven QTLs for height growth, one QTL for stem diameter, one QTL for the height: diameter ratio, one QTL for the number of vegetative buds during flowering time and one QTL for the number of shoots. The estimated magnitude of the QTL effect ranged from 14 to 22% of the total phenotypic variance. One QTL associated with height growth and one affecting the height: diameter ratio were overlapping in the same marker interval with the QTL affecting stem diameter. QTL stability over years was estimated for traits measured in multiple years. Generally, QTLs were only significant in a single year although two QTLs for height growth were close to reaching the significance level in 2 consecutive years.

Journal Article↗
PubMed2003

Mapping of quantitative trait loci controlling adaptive traits in coastal Douglas fir. III. Quantitative trait loci-by-environment interactions.

Quantitative trait loci (QTL) were mapped in the woody perennial Douglas fir (Pseudotsuga menziesii var. menziesii [Mirb.] Franco) for complex traits controlling the timing of growth initiation and growth cessation. QTL were estimated under controlled environmental conditions to identify QTL interactions with photoperiod, moisture stress, winter chilling, and spring temperatures. A three-generation mapping population of 460 cloned progeny was used for genetic mapping and phenotypic evaluations. An all-marker interval mapping method was used for scanning the genome for the presence of QTL and single-factor ANOVA was used for estimating QTL-by-environment interactions. A modest number of QTL were detected per trait, with individual QTL explaining up to 9.5% of the phenotypic variation. Two QTL-by-treatment interactions were found for growth initiation, whereas several QTL-by-treatment interactions were detected among growth cessation traits. This is the first report of QTL interactions with specific environmental signals in forest trees and will assist in the identification of candidate genes controlling these important adaptive traits in perennial plants.

Genetic Linkage↗
PubMed2003

Genetic analysis and genome mapping in Raphanus.

The first genetic map of the Raphanus genome was developed based on meiosis in a hybrid between Raphanus sativus (cultivated radish) and Raphanus raphanistrum (wild radish). This hybrid was used to produce a BC1 population of 54 individuals and an F2 population of 85 individuals. A total of 236 marker loci were assayed in these populations using a set of 144 informative Brassica RFLP probes previously used for genetic mapping in other crucifer species. The genetic maps derived from the BC1 and F2 populations were perfectly collinear and were integrated to produce a robust Raphanus map. Cytological observations demonstrated strict bivalent pairing in the R. sativus x R. raphanistrum hybrids. Productive pairing along the length of each chromosome was confirmed by the identification of nine extensive linkage groups and the lack of clustering of marker loci. Indeed, the distributions of both marker loci and crossovers was more random than those reported for other crop species. The genetic markers and the reference map of Raphanus will be of considerable value for future trait mapping and marker-assisted breeding in this crop, as well as in the intergenomic transfer of Raphanus genes into Brassica crops. The future benefits of comparative mapping with Arabidopsis and Brassica species are also discussed.

Chromosome Mapping↗
PubMedDate not supplied

Parallel computing in interval mapping of quantitative trait loci.

Linear regression analysis is considered the least computationally demanding method for mapping quantitative trait loci (QTL). However, simultaneous search for multiple QTL, the use of permutations to obtain empirical significance thresholds, and larger experimental studies significantly increase the computational demand. This report describes an easily implemented parallel algorithm, which significantly reduces the computing time in both QTL mapping and permutation testing. In the example provided, the analysis time was decreased to less than 15% of a single processor system by the use of 18 processors. We indicate how the efficiency of the analysis could be improved by distributing the computations more evenly to the processors and how other ways of distributing the data facilitate the use of more processors. The use of parallel computing in QTL mapping makes it possible to routinely use permutations to obtain empirical significance thresholds for multiple traits and multiple QTL models. It could also be of use to improve the computational efficiency of the more computationally demanding QTL analysis methods.

Algorithms↗
PubMed2006

Mapping of quantitative trait loci for lactation persistency traits in German Holstein dairy cattle.

A whole genome scan to map quantitative trait loci (QTL) for persistency of milk yield (PMY), persistency of fat yield (PFY), persistency of protein yield (PPY) and persistency of milk energy yield (PEY) was performed in a granddaughter design in the German Holstein dairy cattle population. The analysis included 16 paternal half-sib families with a total of 872 bulls. The analysis was carried out for the first lactation and for the first three lactations combined using univariate weighted multimarker regression. Controlling the false discovery rate across traits and data sets at a level of 0.15 and treating the four persistency traits as different traits revealed 27 significant QTL. A total of 12 chromosomes showed significant QTL effects on a chromosomewise basis. The DGAT1 effect was highly significant for PPY and protein yield. A haplotype analysis using results of previous studies of the same design revealed a co-segregation of various persistency QTL and QTL affecting health traits like dystocia and stillbirth and functional traits like non-return rate 90 and somatic cell score.

Animals↗
PubMed2000

Bayesian mapping of quantitative trait loci for complex binary traits.

A complex binary trait is a character that has a dichotomous expression but with a polygenic genetic background. Mapping quantitative trait loci (QTL) for such traits is difficult because of the discrete nature and the reduced variation in the phenotypic distribution. Bayesian statistics are proved to be a powerful tool for solving complicated genetic problems, such as multiple QTL with nonadditive effects, and have been successfully applied to QTL mapping for continuous traits. In this study, we show that Bayesian statistics are particularly useful for mapping QTL for complex binary traits. We model the binary trait under the classical threshold model of quantitative genetics. The Bayesian mapping statistics are developed on the basis of the idea of data augmentation. This treatment allows an easy way to generate the value of a hypothetical underlying variable (called the liability) and a threshold, which in turn allow the use of existing Bayesian statistics. The reversible jump Markov chain Monte Carlo algorithm is used to simulate the posterior samples of all unknowns, including the number of QTL, the locations and effects of identified QTL, genotypes of each individual at both the QTL and markers, and eventually the liability of each individual. The Bayesian mapping ends with an estimation of the joint posterior distribution of the number of QTL and the locations and effects of the identified QTL. Utilities of the method are demonstrated using a simulated outbred full-sib family. A computer program written in FORTRAN language is freely available on request.

Algorithms↗
PubMed2005

Optimal haplotype structure for linkage disequilibrium-based fine mapping of quantitative trait loci using identity by descent.

A linkage disequilibrium-based method for fine mapping quantitative trait loci (QTL) has been described that uses similarity between individuals' marker haplotypes to determine if QTL alleles are identical by descent (IBD) to model covariances among individuals' QTL alleles for a mixed linear model. Mapping accuracy with this method was found to be sensitive to the number of linked markers that was included in the haplotype when fitting the model at a putative position of the QTL. The objective of this study was to determine the optimal haplotype structure for this IBD-based method for fine mapping a QTL in a previously identified QTL region. Haplotypes consisting of 1, 2, 4, 6, or all 10 available markers were fit as a "sliding window" across the QTL region under ideal and nonideal simulated population conditions. It was found that using haplotypes of 4 or 6 markers as a sliding "window" resulted in the greatest mapping accuracy under nearly all conditions, although the true IBD state at a putative QTL position was most accurately predicted by IBD probabilities obtained using all markers. Using 4 or 6 markers resulted in greater discrimination of IBD probabilities between positions while maintaining sufficient accuracy of IBD probabilities to detect the QTL. Fitting IBD probabilities on the basis of a single marker resulted in the worst mapping accuracy under all conditions because it resulted in poor accuracy of IBD probabilities. In conclusion, for fine mapping using IBD methods, marker information must be used in a manner that results in sensitivity of IBD probabilities to the putative position of the QTL while maintaining sufficient accuracy of IBD probabilities to detect the QTL. Contrary to expectation, use of haplotypes of 4-6 markers to derive IBD probabilities, rather than all available markers, best fits these criteria. Thus for populations similar to those simulated here, optimal mapping accuracy for this IBD-based fine-mapping method is obtained with a haplotype structure including a subset of all available markers.

Crosses, Genetic↗
PubMed1999

High-resolution mapping of quantitative trait loci for sternopleural bristle number in Drosophila melanogaster.

We have mapped quantitative trait loci (QTL) harboring naturally occurring allelic variation for Drosophila bristle number. Lines with high (H) and low (L) sternopleural bristle number were derived by artificial selection from a large base population. Isogenic H and L sublines were extracted from the selection lines, and populations of X and third chromosome H/L recombinant isogenic lines were constructed in the homozygous low line background. The polymorphic cytological locations of roo transposable elements provided a dense molecular marker map with an average intermarker distance of 4.5 cM. Two X chromosome and six chromosome 3 QTL affecting response to selection for sternopleural bristle number and three X chromosome and three chromosome 3 QTL affecting correlated response in abdominal bristle number were detected using a composite interval mapping method. The average effects of bristle number QTL were moderately large, and some had sex-specific effects. Epistasis between QTL affecting sternopleural bristle number was common, and interaction effects were large. Many of the intervals containing bristle number QTL coincided with those mapped in previous studies. However, resolution of bristle number QTL to the level of genetic loci is not trivial, because the genomic regions containing bristle number QTL often did not contain obvious candidate loci, and results of quantitative complementation tests to mutations at candidate loci affecting adult bristle number were ambiguous.

Alleles↗
PubMed2002

Linkage disequilibrium mapping of quantitative trait loci under truncation selection.

As a dense map of single nucleotide polymorphism (SNP) markers are available, population-based linkage disequilibrium (LD) mapping or association study is becoming one of the major tools for identifying quantitative trait loci (QTL) and for fine gene mapping. However, in many cases, LD between the marker and trait locus is not very strong. Approaches that maximize the potential of detecting LD will be essential for the success of LD mapping of QTL. In this paper, we propose two strategies for increasing the probability of detecting LD: (1) phenotypic selection and (2) haplotype LD mapping. To provide the foundations for LD mapping of QTL under selection, we develop analytic tools for assessing the impact of phenotypic selection on allele and haplotype frequencies, and LD under three trait models: single trait locus, two unlinked trait loci, and two linked trait loci with or without epistasis. In addition to a traditional chi(2) test, which compares the difference in allele or haplotype frequencies in the selected sample and population sample, we present multiple regression methods for LD mapping of QTL, and investigate which methods are effective in employing phenotypic selection for QTL mapping. We also develop a statistical framework for investigating and comparing the power of the single marker and multilocus haplotype test for LD mapping of QTL. Finally, the proposed methods are applied to mapping QTL influencing variation in systolic blood pressure in an isolated Chinese population.

Chi-Square Distribution↗
PubMed2006

Mixture cure model with an application to interval mapping of quantitative trait loci.

When censored time-to-event data are used to map quantitative trait loci (QTL), the existence of nonsusceptible subjects entails extra challenges. If the heterogeneous susceptibility is ignored or inappropriately handled, we may either fail to detect the responsible genetic factors or find spuriously significant locations. In this article, an interval mapping method based on parametric mixture cure models is proposed, which takes into consideration of nonsusceptible subjects. The proposed model can be used to detect the QTL that are responsible for differential susceptibility and/or time-to-event trait distribution. In particular, we propose a likelihood-based testing procedure with genome-wide significance levels calculated using a resampling method. The performance of the proposed method and the importance of considering the heterogeneous susceptibility are demonstrated by simulation studies and an application to survival data from an experiment on mice infected with Listeria monocytogenes.

Algorithms↗
PubMed1990

Characterization of H-2 congenic strains using DNA markers.

Congenic mouse strains are widely used in mapping traits to specific loci or short chromosomal regions. The precision of the mapping depends on the information available about the length of the differential segment--the segment introduced from the donor into the background strain. Until recently, very few markers flanking the differential locus were known and consequently the length of the foreign segment could only be determined imprecisely. Now, in an attempt to construct a map of the mouse chromosome 17, we have produced a set of DNA markers distributed along the chromosome. These markers provide a new opportunity to measure the length of the differential segment of the congenic strains and thus increase their usefulness for gene mapping. Here we examined the DNA of 96 H-2 congenic strains using 30 DNA markers; of these, the most proximal is located roughly 1.5 centiMorgans (cM) from the centromere and the most distal is about 20 cM telomeric from the H-2 complex (the complex itself being some 20 cM from the centromere). The mapping depends on polymorphism among the input strains and can therefore establish only the minimal length of the differential segment. This point is emphasized by the fact that the average observed length of the differential segment is only about one half of the expected values.

Alleles↗
PubMed1994

Precision mapping of quantitative trait loci.

Adequate separation of effects of possible multiple linked quantitative trait loci (QTLs) on mapping QTLs is the key to increasing the precision of QTL mapping. A new method of QTL mapping is proposed and analyzed in this paper by combining interval mapping with multiple regression. The basis of the proposed method is an interval test in which the test statistic on a marker interval is made to be unaffected by QTLs located outside a defined interval. This is achieved by fitting other genetic markers in the statistical model as a control when performing interval mapping. Compared with the current QTL mapping method (i.e., the interval mapping method which uses a pair or two pairs of markers for mapping QTLs), this method has several advantages. (1) By confining the test to one region at a time, it reduces a multiple dimensional search problem (for multiple QTLs) to a one dimensional search problem. (2) By conditioning linked markers in the test, the sensitivity of the test statistic to the position of individual QTLs is increased, and the precision of QTL mapping can be improved. (3) By selectively and simultaneously using other markers in the analysis, the efficiency of QTL mapping can be also improved. The behavior of the test statistic under the null hypothesis and appropriate critical value of the test statistic for an overall test in a genome are discussed and analyzed. A simulation study of QTL mapping is also presented which illustrates the utility, properties, advantages and disadvantages of the method.

Chromosome Mapping↗
PubMed2002

Simultaneous detection and fine mapping of quantitative trait loci in mice using heterogeneous stocks.

We describe a method to simultaneously detect and fine map quantitative trait loci (QTL) that is especially suited to the mapping of modifier loci in mouse mutant models. The method exploits the high level of historical recombination present in a heterogeneous stock (HS), an outbred population of mice derived from known founder strains. The experimental design is an F(2) cross between the HS and a genetically distinct line, such as one carrying a knockout or transgene. QTL detection is performed by a standard genome scan with approximately 100 markers and fine mapping by typing the same animals using densely spaced markers over those candidate regions detected by the scan. The analysis uses an extension of the dynamic-programming technique employed previously to fine map QTL in HS mice. We show by simulation that a QTL accounting for 5% of the total variance can be detected and fine mapped with >50% probability to within 3 cM by genotyping approximately 1500 animals.

Animals↗
PubMed1994

Genetic mapping of quantitative trait loci for growth and fatness in pigs.

The European wild boar was crossed with the domesticated Large White pig to genetically dissect phenotypic differences between these populations for growth and fat deposition. The most important effects were clustered on chromosome 4, with a single region accounting for a large part of the breed difference in growth rate, fatness, and length of the small intestine. The study is an advance in genome analyses and documents the usefulness of crosses between divergent outbred populations for the detection and characterization of quantitative trait loci. The genetic mapping of a major locus for fat deposition in the pig could have implications for understanding human obesity.

Adipose Tissue↗
PubMed2004

Mapping multiple quantitative trait Loci for ordinal traits.

Many complex traits in humans and other organisms show ordinal phenotypic variation but do not follow a simple Mendelian pattern of inheritance. These ordinal traits are presumably determined by many factors, including genetic and environmental components. Several statistical approaches to mapping quantitative trait loci (QTL) for such traits have been developed based on a single-QTL model. However, statistical methods for mapping multiple QTL are not well studied as continuous traits. In this paper, we propose a Bayesian method implemented via the Markov chain Monte Carlo (MCMC) algorithm to map multiple QTL for ordinal traits in experimental crosses. We model the ordinal traits under the multiple threshold model, which assumes a latent continuous variable underlying the ordinal phenotypes. The ordinal phenotype and the latent continuous variable are linked through some fixed but unknown thresholds. We adopt a standardized threshold model, which has several attractive features. An efficient sampling scheme is developed to jointly generate the threshold values and the values of latent variable. With the simulated latent variable, the posterior distributions of other unknowns, for example, the number, locations, genetic effects, and genotypes of QTL, can be computed using existing algorithms for normally distributed traits. To this end, we provide a unified approach to mapping multiple QTL for continuous, binary, and ordinal traits. Utility and flexibility of the method are demonstrated using simulated data.

Algorithms↗
PubMed2002

Association mapping, using a mixture model for complex traits.

Association mapping for complex diseases using unrelated individuals can be more powerful than family-based analysis in many settings. In addition, this approach has major practical advantages, including greater efficiency in sample recruitment. Association mapping may lead to false-positive findings, however, if population stratification is not properly considered. In this paper, we propose a method that makes it possible to infer the number of subpopulations by a mixture model, using a set of independent genetic markers and then testing the association between a genetic marker and a trait. The proposed method can be effectively applied in the analysis of both qualitative and quantitative traits. Extensive simulations demonstrate that the method is valid in the presence of a population structure.

Alleles↗
PubMed2003

A haplotype-based algorithm for multilocus linkage disequilibrium mapping of quantitative trait loci with epistasis.

For tightly linked loci, cosegregation may lead to nonrandom associations between alleles in a population. Because of its evolutionary relationship with linkage, this phenomenon is called linkage disequilibrium. Today, linkage disequilibrium-based mapping has become a major focus of recent genome research into mapping complex traits. In this article, we present a new statistical method for mapping quantitative trait loci (QTL) of additive, dominant, and epistatic effects in equilibrium natural populations. Our method is based on haplotype analysis of multilocus linkage disequilibrium and exhibits two significant advantages over current disequilibrium mapping methods. First, we have derived closed-form solutions for estimating the marker-QTL haplotype frequencies within the maximum-likelihood framework implemented by the EM algorithm. The allele frequencies of putative QTL and their linkage disequilibria with the markers are estimated by solving a system of regular equations. This procedure has significantly improved the computational efficiency and the precision of parameter estimation. Second, our method can detect marker-QTL disequilibria of different orders and QTL epistatic interactions of various kinds on the basis of a multilocus analysis. This can not only enhance the precision of parameter estimation, but also make it possible to perform whole-genome association studies. We carried out extensive simulation studies to examine the robustness and statistical performance of our method. The application of the new method was validated using a case study from humans, in which we successfully detected significant QTL affecting human body heights. Finally, we discuss the implications of our method for genome projects and its extension to a broader circumstance. The computer program for the method proposed in this article is available at the webpage http://www.ifasstat.ufl.edu/genome/~LD.

Algorithms↗