scholarly journals An Improved Approach for Mapping Quantitative Trait Loci in a Pseudo-Testcross: Revisiting a Poplar Mapping Study

2010 ◽  
Vol 4 ◽  
pp. BBI.S4153 ◽  
Author(s):  
Song Wu ◽  
Jie Yang ◽  
Youjun Huang ◽  
Yao Li ◽  
Tongming Yin ◽  
...  
Keyword(s):  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Genetic Correlations ◽  
Published Data ◽  
Mapping Study ◽  
Data Set ◽  
Poplar Trees ◽  
Complete Identification ◽  
Trait Loci ◽  
Outcrossing Species

A pseudo-testcross pedigree is widely used for mapping quantitative trait loci (QTL) in outcrossing species, but the model for analyzing pseudo-testcross data borrowed from the inbred backcross design can only detect those QTLs that are heterozygous only in one parent. In this study, an intercross model that incorporates the high heterozygosity and phase uncertainty of outcrossing species was used to reanalyze a published data set on QTL mapping in poplar trees. Several intercross QTLs that are heterozygous in both parents were detected, which are responsible not only for biomass traits, but also for their genetic correlations. This study provides a more complete identification of QTLs responsible for economically important biomass traits in poplars.

scholarly journals A Rank-Based Nonparametric Method for Mapping Quantitative Trait Loci in Outbred Half-Sib Pedigrees: Application to Milk Production in a Granddaughter Design

Genetics ◽  
1998 ◽  
Vol 149 (3) ◽  
pp. 1547-1555 ◽  
Author(s):  
Wouter Coppieters ◽  
Alexandre Kvasz ◽  
Frédéric Farnir ◽  
Juan-Jose Arranz ◽  
Bernard Grisart ◽  
...  
Keyword(s):  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Real Data ◽  
Interval Mapping ◽  
Mapping Method ◽  
Residual Variance ◽  
Data Set ◽  
Wilcoxon Rank Sum Test ◽  
Holstein Friesian ◽  
Trait Loci

Abstract We describe the development of a multipoint nonparametric quantitative trait loci mapping method based on the Wilcoxon rank-sum test applicable to outbred half-sib pedigrees. The method has been evaluated on a simulated dataset and its efficiency compared with interval mapping by using regression. It was shown that the rank-based approach is slightly inferior to regression when the residual variance is homoscedastic normal; however, in three out of four other scenarios envisaged, i.e., residual variance heteroscedastic normal, homoscedastic skewed, and homoscedastic positively kurtosed, the latter outperforms the former one. Both methods were applied to a real data set analyzing the effect of bovine chromosome 6 on milk yield and composition by using a 125-cM map comprising 15 microsatellites and a granddaughter design counting 1158 Holstein-Friesian sires.

Bayesian Model Choice and Search Strategies for Mapping Interacting Quantitative Trait Loci

Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 867-883 ◽  
Author(s):  
Nengjun Yi ◽  
Shizhong Xu ◽  
David B Allison
Keyword(s):  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Complex Traits ◽  
Bayesian Model ◽  
Genetic Model ◽  
Genetic Effects ◽  
Monte Carlo Algorithm ◽  
Data Set ◽  
Epistatic Effects ◽  
Trait Loci

AbstractMost complex traits of animals, plants, and humans are influenced by multiple genetic and environmental factors. Interactions among multiple genes play fundamental roles in the genetic control and evolution of complex traits. Statistical modeling of interaction effects in quantitative trait loci (QTL) analysis must accommodate a very large number of potential genetic effects, which presents a major challenge to determining the genetic model with respect to the number of QTL, their positions, and their genetic effects. In this study, we use the methodology of Bayesian model and variable selection to develop strategies for identifying multiple QTL with complex epistatic patterns in experimental designs with two segregating genotypes. Specifically, we develop a reversible jump Markov chain Monte Carlo algorithm to determine the number of QTL and to select main and epistatic effects. With the proposed method, we can jointly infer the genetic model of a complex trait and the associated genetic parameters, including the number, positions, and main and epistatic effects of the identified QTL. Our method can map a large number of QTL with any combination of main and epistatic effects. Utility and flexibility of the method are demonstrated using both simulated data and a real data set. Sensitivity of posterior inference to prior specifications of the number and genetic effects of QTL is investigated.

A Mixture Model Approach to the Mapping of Quantitative Trait Loci in Complex Populations With an Application to Multiple Cattle Families

Genetics ◽  
1998 ◽  
Vol 148 (1) ◽  
pp. 391-399 ◽  
Author(s):  
Ritsert C Jansen ◽  
David L Johnson ◽  
Johan A M Van Arendonk
Keyword(s):  
Quantitative Trait Loci ◽  
Mixture Model ◽  
Quantitative Trait ◽  
Expectation Maximization Algorithm ◽  
Likelihood Estimation ◽  
Data Set ◽  
Mixture Model Approach ◽  
Trait Loci ◽  
Monte Carlo Em ◽  
Model Approach

Abstract A mixture model approach is presented for the mapping of one or more quantitative trait loci (QTLs) in complex populations. In order to exploit the full power of complete linkage maps the simultaneous likelihood of phenotype and a multilocus (all markers and putative QTLs) genotype is computed. Maximum likelihood estimation in our mixture models is implemented via an Expectation-Maximization algorithm: exact, stochastic or Monte Carlo EM by using a simple and flexible Gibbs sampler. Parameters include allele frequencies of markers and QTLs, discrete or normal effects of biallelic or multiallelic QTLs, and homogeneous or heterogeneous residual variances. As an illustration a dairy cattle data set consisting of twenty half-sib families has been reanalyzed. We discuss the potential which our and other approaches have for realistic multiple-QTL analyses in complex populations.

scholarly journals Mapping Quantitative Trait Loci for Milk Production and Health of Dairy Cattle in a Large Outbred Pedigree

Genetics ◽  
1998 ◽  
Vol 149 (4) ◽  
pp. 1959-1973 ◽  
Author(s):  
Qin Zhang ◽  
Didier Boichard ◽  
Ina Hoeschele ◽  
Cynthia Ernst ◽  
Andre Eggen ◽  
...  
Keyword(s):  
Quantitative Trait Loci ◽  
Dairy Cattle ◽  
Milk Production ◽  
Quantitative Trait ◽  
Genetic Correlations ◽  
Mapping Function ◽  
Chromosome 17 ◽  
Chi Square ◽  
Repulsion Phase ◽  
Trait Loci

Abstract Quantitative trait loci (QTL) affecting milk production and health of dairy cattle were mapped in a very large Holstein granddaughter design. The analysis included 1794 sons of 14 sires and 206 genetic markers distributed across all 29 autosomes and flanking an estimated 2497 autosomal cM using Kosambi's mapping function. All families were analyzed jointly with least-squares (LS) and variance components (VC) methods. A total of 6 QTL exceeding approximate experiment-wise significance thresholds, 24 QTL exceeding suggestive thresholds, and 34 QTL exceeding chromosome-wise thresholds were identified. Significance thresholds were determined via data permutation (for LS analysis) and chi-square distribution (for VC analysis). The average bootstrap confidence interval for the experiment-wise significant QTL was 48 cM. Some chromosomes harbored QTL affecting several traits, and these were always in coupling phase, defined by consistency with genetic correlations among traits. Chromosome 17 likely harbors 2 QTL affecting milk yield, and some other chromosomes showed some evidence for 2 linked QTL affecting the same trait. In each of these cases, the 2 QTL were in repulsion phase in those families appearing to be heterozygous for both QTL, a finding which supports the build-up of linkage disequilibrium due to selection.

scholarly journals Stochastic Search Variable Selection for Identifying Multiple Quantitative Trait Loci

Genetics ◽  
2003 ◽  
Vol 164 (3) ◽  
pp. 1129-1138 ◽  
Author(s):  
Nengjun Yi ◽  
Varghese George ◽  
David B Allison
Keyword(s):  
Quantitative Trait Loci ◽  
Variable Selection ◽  
Quantitative Trait ◽  
Complex Traits ◽  
Stochastic Search ◽  
Model Parameters ◽  
Data Set ◽  
Stochastic Search Variable Selection ◽  
Trait Loci ◽  
Search Variable

AbstractIn this article, we utilize stochastic search variable selection methodology to develop a Bayesian method for identifying multiple quantitative trait loci (QTL) for complex traits in experimental designs. The proposed procedure entails embedding multiple regression in a hierarchical normal mixture model, where latent indicators for all markers are used to identify the multiple markers. The markers with significant effects can be identified as those with higher posterior probability included in the model. A simple and easy-to-use Gibbs sampler is employed to generate samples from the joint posterior distribution of all unknowns including the latent indicators, genetic effects for all markers, and other model parameters. The proposed method was evaluated using simulated data and illustrated using a real data set. The results demonstrate that the proposed method works well under typical situations of most QTL studies in terms of number of markers and marker density.

scholarly journals Multiple Interval Mapping for Quantitative Trait Loci

Genetics ◽  
1999 ◽  
Vol 152 (3) ◽  
pp. 1203-1216
Author(s):  
Chen-Hung Kao ◽  
Zhao-Bang Zeng ◽  
Robert D Teasdale
Keyword(s):  
Genetic Variation ◽  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Genetic Parameters ◽  
Interval Mapping ◽  
Ratio Test ◽  
Data Set ◽  
Multiple Interval Mapping ◽  
Total Genetic Variation ◽  
Trait Loci

Abstract A new statistical method for mapping quantitative trait loci (QTL), called multiple interval mapping (MIM), is presented. It uses multiple marker intervals simultaneously to fit multiple putative QTL directly in the model for mapping QTL. The MIM model is based on Cockerham's model for interpreting genetic parameters and the method of maximum likelihood for estimating genetic parameters. With the MIM approach, the precision and power of QTL mapping could be improved. Also, epistasis between QTL, genotypic values of individuals, and heritabilities of quantitative traits can be readily estimated and analyzed. Using the MIM model, a stepwise selection procedure with likelihood ratio test statistic as a criterion is proposed to identify QTL. This MIM method was applied to a mapping data set of radiata pine on three traits: brown cone number, tree diameter, and branch quality scores. Based on the MIM result, seven, six, and five QTL were detected for the three traits, respectively. The detected QTL individually contributed from ∼1 to 27% of the total genetic variation. Significant epistasis between four pairs of QTL in two traits was detected, and the four pairs of QTL contributed ∼10.38 and 14.14% of the total genetic variation. The asymptotic variances of QTL positions and effects were also provided to construct the confidence intervals. The estimated heritabilities were 0.5606, 0.5226, and 0.3630 for the three traits, respectively. With the estimated QTL effects and positions, the best strategy of marker-assisted selection for trait improvement for a specific purpose and requirement can be explored. The MIM FORTRAN program is available on the worldwide web (http://www.stat.sinica.edu.tw/~chkao/).

Enhanced Efficiency of Quantitative Trait Loci Mapping Analysis Based on Multivariate Complexes of Quantitative Traits

Genetics ◽  
2001 ◽  
Vol 157 (4) ◽  
pp. 1789-1803 ◽  
Author(s):  
Abraham B Korol ◽  
Yefim I Ronin ◽  
Alexander M Itskovich ◽  
Junhua Peng ◽  
Eviatar Nevo
Keyword(s):  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Broad Sense ◽  
Broad Sense Heritability ◽  
Qtl Detection ◽  
Data Set ◽  
Correlated Traits ◽  
Detection Power ◽  
Specific Calculation ◽  
Trait Loci

AbstractAn 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 F2/F3 mapping population of tetraploid wheat (Triticum durum × T. dicoccoides) is provided.

scholarly journals Identification of tissue-specific and common methylation quantitative trait loci in healthy individuals using MAGAR

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Michael Scherer ◽  
Gilles Gasparoni ◽  
Souad Rahmouni ◽  
Tatiana Shashkova ◽  
Marion Arnoux ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Quantitative Trait Loci ◽  
Genetic Variants ◽  
Quantitative Trait ◽  
Healthy Individuals ◽  
Cell Type ◽  
Data Set ◽  
Trait Loci ◽  
Cell Type Specific ◽  
Methylation Quantitative Trait Loci

Abstract Background Understanding the influence of genetic variants on DNA methylation is fundamental for the interpretation of epigenomic data in the context of disease. There is a need for systematic approaches not only for determining methylation quantitative trait loci (methQTL), but also for discriminating general from cell type-specific effects. Results Here, we present a two-step computational framework MAGAR (https://bioconductor.org/packages/MAGAR), which fully supports the identification of methQTLs from matched genotyping and DNA methylation data, and additionally allows for illuminating cell type-specific methQTL effects. In a pilot analysis, we apply MAGAR on data in four tissues (ileum, rectum, T cells, B cells) from healthy individuals and demonstrate the discrimination of common from cell type-specific methQTLs. We experimentally validate both types of methQTLs in an independent data set comprising additional cell types and tissues. Finally, we validate selected methQTLs located in the PON1, ZNF155, and NRG2 genes by ultra-deep local sequencing. In line with previous reports, we find cell type-specific methQTLs to be preferentially located in enhancer elements. Conclusions Our analysis demonstrates that a systematic analysis of methQTLs provides important new insights on the influences of genetic variants to cell type-specific epigenomic variation.

scholarly journals Estimation of Effects of Quantitative Trait Loci in Large Complex Pedigrees

Genetics ◽  
1997 ◽  
Vol 146 (1) ◽  
pp. 409-416 ◽  
Author(s):  
T H E Meuwissen ◽  
M E Goddard
Keyword(s):  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Simulated Data ◽  
Data Set ◽  
Genotype Information ◽  
Trait Loci ◽  
Basic Equations ◽  
Marker Information

A method was derived to estimate effects of quantitative trait loci (QTL) using incomplete genotype information in large outbreeding populations with complex pedigrees. The method accounts for background genes by estimating polygenic effects. The basic equations used are very similar to the usual linear mixed model equations for polygenic models, and segregation analysis was used to estimate the probabilities of the QTL genotypes for each animal. Method R was used to estimate the polygenic heritability simultaneously with the QTL effects. Also, initial allele frequencies were estimated. The method was tested in a simulated data set of 10,000 animals evenly distributed over 10 generations, where 0, 400 or 10,000 animals were genotyped for a candidate gene. In the absence of selection, the bias of the QTL estimates was <2%. Selection biased the estimate of the Aa genotype slightly, when zero animals were genotyped. Estimates of the polygenic heritability were 0.251 and 0.257, in absence and presence of selection, respectively, while the simulated value was 0.25. Although not tested in this study, marker information could be accommodated by adjusting the transmission probabilities of the genotypes from parent to offspring according to the marker information. This renders a QTL mapping study in large multi-generation pedigrees possible.

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