Individual genome sequencing identified a novel enhancer element in exon 7 of the CSFR1 gene by shift of expressed allele ratios

The sequencing of individual genetic information may provide a powerful tool for elucidating the mechanism by which individual SNPs affect promoter function. Here, we assessed the genome of a Russian male that was previously sequenced. The RNA-Seq data from blood cells revealed 234 candidate transcripts with shifts of greater than 1.5-fold from equal biallelic transcription. Of these genes, the CSF1R gene had variations in genic regions that affected the association of RORalpha with its target binding site in vivo. The results of a reporter assay confirmed that a single nucleotide substitution, rs2228422, within the RORalpha recognition motif altered the ability of the enhancer to regulate CSF1R gene transcription. Notably, 31% of Europeans and only 3% of Asians are homozygous for a RORalpha responsive "A" allele, but no association with diseases of rs2228422 has been found thus far.