Mapping the genetic architecture of complex traits in experimental populations

被引:263
作者
Yang, Jian
Zhu, Jun [1 ]
Williams, Robert W.
机构
[1] Zhejiang Univ, Coll Agr Biotechnol, Inst Bioinformat, Hangzhou 310029, Peoples R China
[2] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA
关键词
D O I
10.1093/bioinformatics/btm143
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Understanding how interactions among set of genes affect diverse phenotypes is having a greater impact on biomedical research, agriculture and evolutionary biology. Mapping and characterizing the isolated effects of single quantitative trait locus (QTL) is a first step, but we also need to assemble networks of QTLs and define non-additive interactions (epistasis) together with a host of potential environmental modulators. In this article, we present a full-QTL model with which to explore the genetic architecture of complex trait in multiple environments. Our model includes the effects of multiple QTLs, epistasis, QTL-by-environment interactions and epistasis-by-environment interactions. A new mapping strategy, including marker interval selection, detection of marker interval interactions and genome scans, is used to evaluate putative locations of multiple QTLs and their interactions. All the mapping procedures are performed in the framework of mixed linear model that are flexible to model environmental factors regardless of fix or random effects being assumed. An F-statistic based on Henderson method III is used for hypothesis tests. This method is less computationally greedy than corresponding likelihood ratio test. In each of the mapping procedures, permutation testing is exploited to control for genome-wide false positive rate, and model selection is used to reduce ghost peaks in F-statistic profile. Parameters of the full-QTL model are estimated using a Bayesian method via Gibbs sampling. Monte Carlo simulations help define the reliability and efficiency of the method. Two real-world phenotypes (BXD mouse olfactory bulb weight data and rice yield data) are used as exemplars to demonstrate our methods.
引用
收藏
页码:1527 / 1536
页数:10
相关论文
共 30 条
[1]   Epistasis:: too often neglected in complex trait studies? [J].
Carlborg, Ö ;
Haley, CS .
NATURE REVIEWS GENETICS, 2004, 5 (08) :618-U4
[2]   Expression of Drosophila mushroom body mutations in alternative genetic backgrounds: A case study of the mushroom body miniature gene (mbm) [J].
deBelle, JS ;
Heisenberg, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (18) :9875-9880
[3]  
Doerge RW, 1996, GENETICS, V142, P285
[4]   Complex interactions of new quantitative trait loci, Sluc1, Sluc2, Sluc3, and Sluc4, that influence the susceptibility to lung cancer in the mouse [J].
Fijneman, RJA ;
deVries, SS ;
Jansen, RC ;
Demant, P .
NATURE GENETICS, 1996, 14 (04) :465-467
[5]   Gene-targeting studies of mammalian behavior: Is it the mutation or the background genotype? [J].
Gerlai, R .
TRENDS IN NEUROSCIENCES, 1996, 19 (05) :177-181
[6]   Opinion - The flexible genome [J].
Greenspan, RJ .
NATURE REVIEWS GENETICS, 2001, 2 (05) :383-387
[7]  
Gurganus MC, 1999, GENETICS, V152, P1585
[8]   A SIMPLE REGRESSION METHOD FOR MAPPING QUANTITATIVE TRAIT LOCI IN LINE CROSSES USING FLANKING MARKERS [J].
HALEY, CS ;
KNOTT, SA .
HEREDITY, 1992, 69 :315-324
[9]   RFLP mapping of isozymes, RAPD and QTLs for grain shape, brown planthopper resistance in a doubled haploid rice population [J].
Huang, N ;
Parco, A ;
Mew, T ;
Magpantay, G ;
McCouch, S ;
Guiderdoni, E ;
Xu, JC ;
Subudhi, P ;
Angeles, ER ;
Khush, GS .
MOLECULAR BREEDING, 1997, 3 (02) :105-113
[10]  
JANS DA, 1994, FASEB J, V11, P871