Figure 3.
Linkage disequilibrium of BHLHE40 by ancestry. Linkage (r2) of BHLHE40 SNP rs11130215 is shown as an example for the haplotype group, compiled and edited from SNAP plots48 for CEU, CHBJPT, and YRI ancestry groups within the 1000 Genome Pilot 1 data base (hg18 locations). The range plotted is from 25K 5' to the SNP (just at the limit of CEU significant linkage) to 25K 3' to the SNP. The sample with CEU ancestry had far stronger 5' linkage than the Asian or YRI samples, but linkage dropped sharply within a few thousand nucleotides downstream of the 3' UTR in all groups. BHLHE40 is a small gene (green arrow). Its protein binds to E-box transcription factor binding sites of several circadian genes, deactivating promoter activity by competitive inhibition.45,56 BHLHE40 forms heterodimers with BHLHE41. BHLHE40 transcription is enhanced by light pulses, probably due to a CRE-responsive element in its promoter. According to the Scripps Genome Adviser,49 several of the BHLHE40-associated alleles may influence transcription binding sites of the adjacent gene.