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A positive and negative ΔSV implies that the alternative allele will result in a gain or loss of binding affinity, respectively. Nt is the total number of experimentally validated binding sequences for each TFBS in the TRANSFAC database; bij is the number of counts of the i-th nucleotide at the j-th position in the PWM; and di represents the percentage of the i-th nucleotide (A, C, G or T) in the human genome. We applied our method to a region on chromosome 1q that had previously been found through linkage and association analysis to harbor genetic factors that contribute to the variation of femoral neck and lumbar spine bone mineral density (BMD) in premenopausal white women (Ichikawa et 일본자막야동 al., 2008). However, this algorithm does not consider sequence features of protein–DNA binding sites, and requires gene expression data, which is not always available for a given tissue and, more importantly, in the right biological contex


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It is especially valuable for prioritizing candidate SNPs identified by the GWAS, or novel or rare variants discovered from the direct human genome sequencing. Promoter regions were used as an example of regulatory regions to illustrate the procedures involved. In this study, we proposed a three-step bioinformatics approach to identify functional SNPs within the regulatory regions following GWAS. It has been reported that E2F1 can serve as both positive and negative regulator on their target genes (Crowe et al., 2001; Croxton et al., 2002; Stanelle et al., 2002). Consistent with this interpretation, the expression level of the TPM3 gene was found to be low in kidney cells and in all fetal tissues, as documented in the microarray gene expression database at the UCSC Genome Browser website (Fujita et al., 2011). A total of 869 genes were retrieved using IPA software by querying bone-related genes in the system (Supplementary Data 3