scholarly journals Is the Genotype-Phenotype Map Modular?: A Statistical Approach Using Mouse Quantitative Trait Loci Data

Genetics ◽  
2000 ◽  
Vol 156 (1) ◽  
pp. 305-311 ◽  
Author(s):  
Jason G Mezey ◽  
James M Cheverud ◽  
Günter P Wagner
Keyword(s):  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Statistical Approach ◽  
Genetic Effects ◽  
Statistical Distribution ◽  
Data Set ◽  
Alveolar Region ◽  
Phenotypic Characters ◽  
Statistical Support ◽  
Complex Characters

Abstract Various theories about the evolution of complex characters make predictions about the statistical distribution of genetic effects on phenotypic characters, also called the genotype-phenotype map. With the advent of QTL technology, data about these distributions are becoming available. In this article, we propose simple tests for the prediction that functionally integrated characters have a modular genotype-phenotype map. The test is applied to QTL data on the mouse mandible. The results provide statistical support for the notion that the ascending ramus region of the mandible is modularized. A data set comprising the effects of QTL on a more extensive portion of the phenotype is required to determine if the alveolar region of the mandible is also modularized.

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.

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.

ADDO: a comprehensive toolkit to detect, classify and visualize additive and non-additive quantitative trait loci

2019 ◽  
Vol 36 (5) ◽  
pp. 1517-1521
Author(s):  
Leilei Cui ◽  
Bin Yang ◽  
Nikolas Pontikos ◽  
Richard Mott ◽  
Lusheng Huang
Keyword(s):  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Association Studies ◽  
Genetic Effects ◽  
Supplementary Information ◽  
Genome Wide Association Studies ◽  
Additive Effects ◽  
A Genome ◽  
Trait Loci ◽  
Additive Genetic Effects

Abstract Motivation During the past decade, genome-wide association studies (GWAS) have been used to map quantitative trait loci (QTLs) underlying complex traits. However, most GWAS focus on additive genetic effects while ignoring non-additive effects, on the assumption that most QTL act additively. Consequently, QTLs driven by dominance and other non-additive effects could be overlooked. Results We developed ADDO, a highly efficient tool to detect, classify and visualize QTLs with additive and non-additive effects. ADDO implements a mixed-model transformation to control for population structure and unequal relatedness that accounts for both additive and dominant genetic covariance among individuals, and decomposes single-nucleotide polymorphism effects as either additive, partial dominant, dominant or over-dominant. A matrix multiplication approach is used to accelerate the computation: a genome scan on 13 million markers from 900 individuals takes about 5 h with 10 CPUs. Analysis of simulated data confirms ADDO’s performance on traits with different additive and dominance genetic variance components. We showed two real examples in outbred rat where ADDO identified significant dominant QTL that were not detectable by an additive model. ADDO provides a systematic pipeline to characterize additive and non-additive QTL in whole genome sequence data, which complements current mainstream GWAS software for additive genetic effects. Availability and implementation ADDO is customizable and convenient to install and provides extensive analytics and visualizations. The package is freely available online at https://github.com/LeileiCui/ADDO. Supplementary information Supplementary data are available at Bioinformatics online.

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 Accuracy of marker-assisted selection with single markers and marker haplotypes in cattle

2007 ◽  
Vol 89 (4) ◽  
pp. 215-220 ◽  
Author(s):  
B. J. HAYES ◽  
A. J. CHAMBERLAIN ◽  
H. McPARTLAN ◽  
I. MACLEOD ◽  
L. SETHURAMAN ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Quantitative Trait Loci ◽  
Single Nucleotide Polymorphisms ◽  
Quantitative Trait ◽  
Marker Assisted Selection ◽  
Nucleotide Polymorphisms ◽  
Data Set ◽  
Single Nucleotide ◽  
Angus Cattle ◽  
Genome Wide

SummaryA key question for the implementation of marker-assisted selection (MAS) using markers in linkage disequilibrium with quantitative trait loci (QTLs) is how many markers surrounding each QTL should be used to ensure the marker or marker haplotypes are in sufficient linkage disequilibrium (LD) with the QTL. In this paper we compare the accuracy of MAS using either single markers or marker haplotypes in an Angus cattle data set consisting of 9323 genome-wide single nucleotide polymorphisms (SNPs) genotyped in 379 Angus cattle. The extent of LD in the data set was such that the average marker–marker r2 was 0·2 at 200 kb. The accuracy of MAS increased as the number of markers in the haplotype surrounding the QTL increased, although only when the number of markers in the haplotype was 4 or greater did the accuracy exceed that achieved when the SNP in the highest LD with the QTL was used. A large number of phenotypic records (>1000) were required to accurately estimate the effects of the haplotypes.

Genetic Effects on Bone Mechanotransduction in Congenic Mice Harboring Bone Size and Strength Quantitative Trait Loci

2007 ◽  
Vol 22 (7) ◽  
pp. 984-991 ◽  
Author(s):  
Alexander G Robling ◽  
Stuart J Warden ◽  
Kathryn L Shultz ◽  
Wesley G Beamer ◽  
Charles H Turner
Keyword(s):  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Genetic Effects ◽  
Bone Size ◽  
Congenic Mice ◽  
Trait Loci

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 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/).

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