Mapping Quantitative Trait Loci in a Non-Equilibrium Population

The genetic control of a complex trait can be studied by testing and mapping the genotypes of the underlying quantitative trait loci (QTLs) through their associations with observable marker genotypes. All existing statistical methods for QTL mapping assume an equilibrium population, allowing marker-QTL associations to be simply described at the gametic level. However, many mapping populations in practice may deviate from equilibrium; thus, gametic associations cannot reflect marker-QTL associations at the genotype level. We develop a robust model for mapping QTLs in a non-equilibrium natural population in which individuals are not necessarily randomly mating due to various evolutionary forces. Without use of Hardy-Weinberg equilibrium, the new model founds marker-QTL associations directly on the genotypes, specified by a group of disequilibrium parameters. Simulation studies were performed to test the statistical properties of the model, which suggests that the new model covers current mapping models and can be safely used for any data set.

[1]  P. Hedrick,et al.  Gametic disequilibrium measures: proceed with caution. , 1987, Genetics.

[2]  J. Ott.  Genetic data analysis II , 1997 .

[3]  Terry L King.  A Guide to Chi-Squared Testing , 1997 .

[4]  Rong‐Cai Yang.  Analysis of multilocus zygotic associations. , 2002, Genetics.

[5]  N. Morton,et al.  Hardy–Weinberg quality control , 1999, Annals of human genetics.

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

[7]  R. Lewontin.  The Interaction of Selection and Linkage. I. General Considerations; Heterotic Models. , 1964, Genetics.

[8]  S. Wahlund.  ZUSAMMENSETZUNG VON POPULATIONEN UND KORRELATIONSERSCHEINUNGEN VOM STANDPUNKT DER VERERBUNGSLEHRE AUS BETRACHTET , 2010 .

[9]  L. Kruglyak.  Prospects for whole-genome linkage disequilibrium mapping of common disease genes , 1999, Nature Genetics.

[10]  Z B Zeng,et al.  Joint linkage and linkage disequilibrium mapping in natural populations. , 2001, Genetics.

[11]  Ian Purvis,et al.  Detection of genotyping errors by Hardy–Weinberg equilibrium testing , 2004, European Journal of Human Genetics.

[12]  J. Haldane,et al.  The association of characters as a result of inbreeding and linkage. , 1949, Annals of eugenics.

[13]  Rongling Wu,et al.  A haplotype-based algorithm for multilocus linkage disequilibrium mapping of quantitative trait loci with epistasis. , 2003, Genetics.

[14]  A. McRae,et al.  Linkage disequilibrium in domestic sheep. , 2002, Genetics.

[15]  Jacqueline K. Wittke-Thompson,et al.  Rational inferences about departures from Hardy-Weinberg equilibrium. , 2005, American journal of human genetics.

[16]  B. Charlesworth,et al.  The evolution of sex chromosomes. , 1991, Science.

[17]  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.

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

[19]  R. Yang.  Zygotic associations and multilocus statistics in a nonequilibrium diploid population. , 2000, Genetics.

[20]  G. Casella,et al.  Joint linkage and linkage disequilibrium mapping of quantitative trait loci in natural populations. , 2002, Genetics.

[21]  Jeff Price.  Hybrid Zones and the Evolutionary Process , 1993 .

[22]  F. Binet,et al.  Association between mendelian factors with mixed selfing and random mating , 1956, Heredity.