Comparison between various strategies for the disease-gene mapping using linkage disequilibrium analyses: studies on adenine phosphoribosyltransferase deficiency used as an example.
Recently, linkage disequilibrium analyses have been used to detect disease-causing loci based on the common disease-common variant hypothesis. To see what methods can effectively identify the genes, we have to apply them to the practical data obtained from the human population. We extensively performed linkage disequilibrium and haplotype analyses on adenine phosphoribosyltransferase ( APRT) genes in both control and deficient subjects. To examine the power to detect disease-causing loci, we analyzed SNPs, STRPs, and VNTR within and around the APRT gene. When only SNPs were used, P values did not necessarily show significant difference, even at loci close to the mutation site for APRT*J that is exclusively observed among Japanese. However, the examination of the same samples with haplotypes based on the haplotype block data gave sufficient significance. In the case of STRP and VNTR, some single-marker loci showed significant difference. Our study suggested that the use of haplotype analysis based on the haplotype-block structure is more powerful than single-marker locus analysis for the detection of disease-related loci.
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan. omoikane@tri-kobe.org.|Laboratory for Clinical Genome Informatics, Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. omoikane@tri-kobe.org.
Shin-Ichi
SI
Kuno
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
Atsuo
A
Taniguchi
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.|Advanced Research Laboratory, Hitachi Ltd., Tokyo, Japan.
Akira
A
Saito
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
Sanae
S
Tsuchida-Otsuka
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.|Division of Genomic Medicine, Department of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.
Naoyuki
N
Kamatani
D000228:Adenine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics*; D001499:Bayes Theorem; D016022:Case-Control Studies; D002874:Chromosome Mapping / Q000379:methods*; D017931:DNA Primers; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics*
D017931:DNA Primers; D005819:Genetic Markers; D000228:Adenine Phosphoribosyltransferase