Fundamental Research Division
The DRF at the CEA assemble approximately 6,000 scientists since January 2016.
Scientific result | Genetic diseases | Cellular mechanisms
Non-coding regions of the genome appear to reduce
the severity of two red blood cell diseases: beta thalassemias and
sickle cell anemia. Researchers at the CEA-IRCM, in collaboration with
English and Dutch laboratories, have elucidated mechanisms explaining
how non-coding DNA sequences exert their action to improve symptoms of
these two diseases.
Beta thalassemias and sickle cell anemia are among the most
common hereditary disorders affecting red blood cells. These disorders are
caused by mutations in the β globin gene, leading to alterations in adult
hemoglobin. Many factors can alter their gravity, in particular the
ability of some patients to produce fetal hemoglobin, which is normally kept
‘silent’ in adults. In some individuals, this hemoglobin ‘escapes’ this natural
suppression without any consequence to their health. However, specifically in
patients with thalassemias and sickle cell anemia, it produces a beneficial
effect by compensating for the adult hemoglobin defects.
regions of the genome, formerly called “junk DNA”, now have a recognized
role in gene regulation. Their mutations or variations may thus be involved in
the occurrence or severity of many diseases (e.g. diabetes, cardiovascular
diseases, and cancers). More than 10 years ago, genetic variants associated with
the production of fetal hemoglobin were identified in adults, located in a
non-coding ‘genetic desert’ on chromosome 6q23, tens of thousands of base
pairs away from the closest genes.
Starting with samples taken from thalassemic
patients, the researchers combined the use of techniques for analyzing
chromosome folding with high-throughput analyses of DNA to elucidate the
molecular mechanisms that explain how non-coding variants exert their action and
improve the symptoms of thalassemias and sickle cell anemia.
showed that in a normal context these variants physically interact with the MYB
gene more than 80,000 base pairs away, thanks to the folding of chromosomes.
However, in patients with beta-thalassemias or sickle cell anemia and carriers
of these variants, there is a decrease in chromosomal folds. The variants access
the MYB gene with more difficulty and activate it less efficiently. This
decreased expression in thalassemic patients and carriers of these variants
leads to a reactivation of healthy fetal globins, enabling the recreation of a
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.