PMC:1079843 / 18898-21280 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/1079843","sourcedb":"PMC","sourceid":"1079843","source_url":"http://www.ncbi.nlm.nih.gov/pmc/1079843","text":"Pairwise linkage disequilibrium (LD) measurement and haplotype analyses\nThe size of the human TPH1 gene is about 29 kb and the LD between all pairs of 10 SNP markers in all subjects was estimated using the SNP Alyze® program (Table 3). The data above and below the diagonal line in Table 3 show, respectively, the results of the pairwise LD analysis, as indicated by the D' [38]; a higher value indicating a higher degree of LD), and the p value for the chi-squared test. As shown in Table 3, the D' values ranges from 0.032 to 1 and the majority of the D' value is greater than 0.5. These data suggested that sequence variants within the TPH1 gene are in strong disequilibrium (the upper diagonal of the Table 3). Furthermore, as indicated by the lower diagonal of Table 3, statistically significant LD was detected for almost all marker pairs among these SNPs. Few exceptions were observed for marker pairs T3840A / A-1067G, A27237 / G-347T, and A27237 / GA12517C in which the D' values are 0.076, 0.032, and 0.039, respectively.\nHaplotypes constructed using the PHASE 2.0 program [39] revealed a total of 70 haplotypes in combined controls and patients (data not shown). Among these haplotypes, the majority is in very low frequency but the four major haplotypes with frequency greater than 2% are found in 59.8% of the total population. Estimation of haplotype distribution and the Fisher's exact test values for testing the significance of differences in individual haplotype frequencies between case and control groups for the haplotypes with frequency \u003e 2% in at least one group were listed in Table 4. Additional test was performed to assess overall haplotype frequency profile differences, rather than frequency differences for a specific haplotype, and p value estimated from 1000 permutation tests was also obtained (Table 4). Although a trend of significance was detected for the GGGAGACCCA haplotype between the case and control groups (p = 0.028) and few haplotypes showed slightly increased risks in which the value of odds ratios are larger than 2, the significances were abolished after Bonferroni correction for multiple tests thus suggested the effect is minor (Table 4). Furthermore, the overall comparison for all haplotypes between two groups was not significant (p = 0.082) and the p value from 1000 time permutation test was also not significant (p = 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