Mapping of complex traits by single-nucleotide polymorphisms.
Molecular geneticists are developing the third-generation human genome map with single-nucleotide polymorphisms (SNPs), which can be assayed via chip-based microarrays. One use of these SNP markers is the ability to locate loci that may be responsible for complex traits, via linkage/linkage-disequilibrium analysis. In this communication, we describe a semiparametric method for combined linkage/linkage-disequilibrium analysis using SNP markers. Asymptotic results are obtained for the estimated parameters, and the finite-sample properties are evaluated via a simulation study. We also applied this technique to a simulated genome-scan experiment for mapping a complex trait with two major genes. This experiment shows that separate linkage and linkage-disequilibrium analyses correctly detected the signals of both major genes; but the rates of false-positive signals seem high. When linkage and linkage-disequilibrium signals were combined, the analysis yielded much stronger and clearer signals for the presence of two major genes than did two separate analyses.
Zhao
L P
LP
Quantitative Genetic Epidemiology Group, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. lzhao@fhcrc.org
Aragaki
C
C
Hsu
L
L
Quiaoit
F
F
D015374:Biosensing Techniques; D002874:Chromosome Mapping / Q000379:methods* / Q000706:statistics & numerical data; D030342:Genetic Diseases, Inborn / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008957:Models, Genetic; D009711:Nucleotides / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics*
D005819:Genetic Markers; D009711:Nucleotides