title: Haplotyping a quantitative trait with a high-density map in experimental crosses.
abstract: BACKGROUND
  The ultimate goal of genetic mapping of quantitative trait loci (QTL) is the positional cloning of genes involved in any agriculturally or medically important phenotype. However, only a small portion (< or = 1%) of the QTL detected have been characterized at the molecular level, despite the report of hundreds of thousands of QTL for different traits and populations.
  
  
  RESULTS
  We develop a statistical model for detecting and characterizing the nucleotide structure and organization of haplotypes that underlie QTL responsible for a quantitative trait in an F2 pedigree. The discovery of such haplotypes by the new model will facilitate the molecular cloning of a QTL. Our model is founded on population genetic properties of genes that are segregating in a pedigree, constructed with the mixture-based maximum likelihood context and implemented with the EM algorithm. The closed forms have been derived to estimate the linkage and linkage disequilibria among different molecular markers, such as single nucleotide polymorphisms, and quantitative genetic effects of haplotypes constructed by non-alleles of these markers. Results from the analysis of a real example in mouse have validated the usefulness and utilization of the model proposed.
  
  
  CONCLUSIONS
  The model is flexible to be extended to model a complex network of genetic regulation that includes the interactions between different haplotypes and between haplotypes and environments.
authors: Department of Epidemiology and Health Policy Research, University of Florida, Gainesville, Florida, United States of America.
authors: Wei
authors: W
authors: Hou
authors: John Stephen F
authors: JS
authors: Yap
authors: Song
authors: S
authors: Wu
authors: Tian
authors: T
authors: Liu
authors: James M
authors: JM
authors: Cheverud
authors: Rongling
authors: R
authors: Wu
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005838:Genotype; D006239:Haplotypes; D015810:Linkage Disequilibrium; D051379:Mice; D008957:Models, Genetic; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
references: Genet Res. 1999 Dec;74(3):313-22
references: 10689807
references: Genome Res. 2007 Jan;17(1):88-95
references: 17095708
references: Nat Rev Genet. 2001 Jan;2(1):11-20
references: 11253063
references: Pharmacogenomics. 2000 Feb;1(1):15-26
references: 11258593
references: Pharmacogenomics. 2001 Feb;2(1):11-24
references: 11258193
references: Science. 2001 Nov 23;294(5547):1719-23
references: 11721056
references: Proc Natl Acad Sci U S A. 2002 May 28;99(11):7335-9
references: 12032283
references: Genetics. 2003 Apr;163(4):1533-48
references: 12702696
references: Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9900-5
references: 12900503
references: Genetics. 2004 Sep;168(1):503-11
references: 15454560
references: Genetics. 1989 Jan;121(1):185-99
references: 2563713
references: Genetics. 1994 Apr;136(4):1447-55
references: 8013917
references: Genetics. 1994 Apr;136(4):1457-68
references: 8013918
references: Science. 1994 Sep 30;265(5181):2037-48
references: 8091226
references: Genetics. 1994 Nov;138(3):963-71
references: 7851788
references: Genetics. 1999 Jul;152(3):1203-16
references: 10388834
references: Nat Rev Genet. 2005 Apr;6(4):271-86
references: 15803197
references: Science. 2006 Mar 31;311(5769):1936-9
references: 16527928
references: Science. 2000 Jul 7;289(5476):85-8
references: 10884229