Human haemoglobin genetics

The genes which direct the structure of human fetal and adult haemoglobin consist of a linked pair of alpha-chain loci on chromosome 16 and the G gamma-A gamma-delta-beta loci complex on chromosome 11. The delta-and beta-chain genes contain inserts similar to those of the mouse and rabbit globin genes. The structure of the various messenger RNAs transcribed from these loci is now worked out although the function of the non-coding regions is not known. The abnormal haemoglobin disorders and thalassaemias result from a variety of lesions at these loci which include single base substitutions, deletions of one or more bases or entire loci, insertions, frame-shifts, fusion genes caused by abnormal crossing over, chain termination mutations and ill-defined defects which lead to a reduced rate of transcription or abnormal structure of messenger RNA. Some progress has been made towards an understanding of the cellular mechanisms whereby the haemoglobin polymorphisms have been maintained. Very little is known about the regulatory mechanisms involved in the switch from fetal to adult haemoglobin production, although it is likely that certain specific areas of the gamma-delta-beta gene complex are involved in its control.