Haplotyping a quantitative trait with a high-density map in experimental crosses.
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.
Hou
Wei
W
Department of Epidemiology and Health Policy Research, University of Florida, Gainesville, Florida, United States of America.
Yap
John Stephen F
JS
Wu
Song
S
Liu
Tian
T
Cheverud
James M
JM
Wu
Rongling
R
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
Genet Res. 1999 Dec;74(3):313-22
10689807
Genome Res. 2007 Jan;17(1):88-95
17095708
Nat Rev Genet. 2001 Jan;2(1):11-20
11253063
Pharmacogenomics. 2000 Feb;1(1):15-26
11258593
Pharmacogenomics. 2001 Feb;2(1):11-24
11258193
Science. 2001 Nov 23;294(5547):1719-23
11721056
Proc Natl Acad Sci U S A. 2002 May 28;99(11):7335-9
12032283
Genetics. 2003 Apr;163(4):1533-48
12702696
Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9900-5
12900503
Genetics. 2004 Sep;168(1):503-11
15454560
Genetics. 1989 Jan;121(1):185-99
2563713
Genetics. 1994 Apr;136(4):1447-55
8013917
Genetics. 1994 Apr;136(4):1457-68
8013918
Science. 1994 Sep 30;265(5181):2037-48
8091226
Genetics. 1994 Nov;138(3):963-71
7851788
Genetics. 1999 Jul;152(3):1203-16
10388834
Nat Rev Genet. 2005 Apr;6(4):271-86
15803197
Science. 2006 Mar 31;311(5769):1936-9
16527928
Science. 2000 Jul 7;289(5476):85-8
10884229