A Statistical Variance Components Framework for Mapping Imprinted Quantitative Trait Locus in Experimental Crosses

Current methods for mapping imprinted quantitative trait locus (iQTL) with inbred line crosses assume fixed QTL effects. When an iQTL segregates in experimental line crosses, combining different line crosses with similar genetic background can improve the accuracy of iQTLs inference. In this article, we develop a general interval-based statistical variance components framework to map iQTLs underlying complex traits by combining different backcross line crosses. We propose a new iQTL variance partition method based on the nature of marker alleles shared identical-by-decent (IBD) in inbred lines. Maternal effect is adjusted when testing imprinting. Efficient estimation methods with the maximum likelihood and the restricted maximum likelihood are derived and compared. Statistical properties of the proposed mapping strategy are evaluated through extensive simulations under different sampling designs. An extension to multiple QTL analysis is given. The proposed method will greatly facilitate genetic dissection of imprinted complex traits in inbred line crosses.

[1]  N. Schork,et al.  Testing the robustness of the likelihood-ratio test in a variance-component quantitative-trait loci-mapping procedure. , 1999, American journal of human genetics.

[2]  Shizhong Xu,et al.  A random model approach to interval mapping of quantitative trait loci. , 1995, Genetics.

[3]  R. Jansen,et al.  Controlling the type I and type II errors in mapping quantitative trait loci. , 1994, Genetics.

[4]  W Davies,et al.  Multiple marker mapping of quantitative trait loci in a cross between outbred wild boar and large white pigs. , 1998, Genetics.

[5]  R. Hanson,et al.  Assessment of parent-of-origin effects in linkage analysis of quantitative traits. , 2001, American journal of human genetics.

[6]  Aaas News,et al.  Book Reviews , 1893, Buffalo Medical and Surgical Journal.

[7]  C. Amos Robust variance-components approach for assessing genetic linkage in pedigrees. , 1994, American journal of human genetics.

[8]  K. Liang,et al.  Asymptotic Properties of Maximum Likelihood Estimators and Likelihood Ratio Tests under Nonstandard Conditions , 1987 .

[9]  R. Jansen,et al.  Interval mapping of multiple quantitative trait loci. , 1993, Genetics.

[10]  J. Cheverud Genetics and analysis of quantitative traits , 1999 .

[11]  S. R. Searle,et al.  A Comparison of Variance Component Estimators , 1976 .

[12]  Rongling Wu,et al.  A general statistical framework for mapping quantitative trait loci in nonmodel systems: issue for characterizing linkage phases. , 2003, Genetics.

[13]  M. Groenen,et al.  Genome-wide scan for body composition in pigs reveals important role of imprinting. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[14]  R. N. Curnow,et al.  Estimating the locations and the sizes of the effects of quantitative trait loci using flanking markers , 1992, Theoretical and Applied Genetics.

[15]  M S McPeek,et al.  Estimation of variance components of quantitative traits in inbred populations. , 2000, American journal of human genetics.

[16]  Rongling Wu,et al.  A random model for mapping imprinted quantitative trait loci in a structured pedigree: an implication for mapping canine hip dysplasia. , 2007, Genomics.

[17]  John A. Nelder,et al.  A Simplex Method for Function Minimization , 1965, Comput. J..

[18]  Rongling Wu,et al.  Statistical Genetics of Quantitative Traits: Linkage, Maps and QTL , 2007 .

[19]  David BotsteinS’B Mapping Mendelian Factors Underlying Quantitative Traits Using RFLP Linkage Maps , 2002 .

[20]  S. Xu,et al.  Combining different line crosses for mapping quantitative trait loci using the identical by descent-based variance component method. , 1998, Genetics.

[21]  K. Pfeifer,et al.  Mechanisms of genomic imprinting. , 2000, American journal of human genetics.

[22]  Z B Zeng,et al.  Theoretical basis for separation of multiple linked gene effects in mapping quantitative trait loci. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[23]  M. Lynch,et al.  Genetics and Analysis of Quantitative Traits , 1996 .

[24]  D. L. Harris,et al.  GENOTYPIC COVARIANCES BETWEEN INBRED RELATIVES. , 1964, Genetics.

[25]  D Siegmund,et al.  Statistical methods for mapping quantitative trait loci from a dense set of markers. , 1999, Genetics.

[26]  Z. Zeng,et al.  Multiple interval mapping for quantitative trait loci. , 1999, Genetics.

[27]  Henk Bovenhuis,et al.  On the detection of imprinted quantitative trait loci in experimental crosses of outbred species. , 2002, Genetics.

[28]  Z. Zeng Precision mapping of quantitative trait loci. , 1994, Genetics.

[29]  R. Doerge,et al.  Empirical threshold values for quantitative trait mapping. , 1994, Genetics.

[30]  Rongling Wu,et al.  A Statistical Model for Estimating Maternal-Zygotic Interactions and Parent-of-Origin Effects of QTLs for Seed Development , 2008, PloS one.

[31]  L. Almasy,et al.  Multipoint quantitative-trait linkage analysis in general pedigrees. , 1998, American journal of human genetics.

[32]  Burt,et al.  Genes in Conflict , 2008 .

[33]  Yuehua Cui,et al.  A statistical framework for genome-wide scanning and testing of imprinted quantitative trait loci. , 2007, Journal of theoretical biology.

[34]  Rongling Wu,et al.  A statistical model for dissecting genomic imprinting through genetic mapping , 2007, Genetica.

[35]  H. D. Patterson,et al.  Recovery of inter-block information when block sizes are unequal , 1971 .

[36]  Rongling Wu,et al.  Model for mapping imprinted quantitative trait loci in an inbred F2 design. , 2006, Genomics.