One further trans-association is of particular interest. Prolongation of fetal gamma hemoglobin expression in adults is often observed in thalassemia patients. We found association of two probes that detect both HBG1 and HBG2 transcripts from 11p15 with rs766432 in the second intron of the BCL11A zinc finger proto-oncogene at 2p16. This same SNP has previously been associated with the fraction of erythrocytes that contain measurable fetal hemoglobin31, and alteration of BCL11A activity was recently shown drive differences in globin switching between mice and humans32. Another SNP in BCL11A, rs4671393 has been associated with abundance of two BCL11A transcript isoforms in CEU and YRI HapMap lymphoblast cell lines33, but is not associated with BCL11A transcript abundance in our leukocyte data, suggesting that regulation of BCL11A translation or protein activity is more likely to be affecting HBG expression in our sample.
