Genetic disorders of human haemoglobin as models for analysing gene regulation.
The genetic and acquired disorders of human haemoglobin provide a diverse group of naturally occurring models for analysing the regulation of protein synthesis. They include structural haemoglobin variants, thalassaemias, which are conditions in which there is a reduced rate of globin chain production, and hereditary persistence of foetal haemoglobin (HPFH) in which there is an inherited abnormality in the switch from foetal to adult haemoglobin synthesis. The thalassaemias result from a diverse series of cis acting lesions of the globin genes which include deletions, insertions, frame shift mutations, and point mutations involving transcription, messenger RNA processing, initiation, termination, poly A addition and globin chain stability. Many forms of HPFH are due to deletions of the beta-like gene cluster; it has been suggested that they may involve regions of the cluster which are involved in the regulation of the foetal to adult globin chain switch. So far, however, no regions of this type have been identified with certainty. The varieties of HPFH not associated with major gene deletions, or those caused by genetic determinants that are not linked to the globin gene clusters, and some of the acquired forms of alpha thalassaemia associated with mental retardation or leukaemia, may be more useful models for studying the regulation of the globin genes, particularly their developmental control.
D001483:Base Sequence; D002872:Chromosome Deletion; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics; D005796:Genes; D006441:Hemoglobin A / Q000235:genetics; D006454:Hemoglobins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008297:Male; D010641:Phenotype; D013789:Thalassemia / Q000235:genetics*
D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D006441:Hemoglobin A; D005319:Fetal Hemoglobin