Recent genome wide association studies (GWAS) have identified several chromosomal loci responsible for the regulation of fetal hemoglobin (HbF) that are associated with the hereditary persistence of HbF (HPFH) in the adult life. Major new loci lie on chromosome 2,6 and 13. The first locus maps on the BCL11A gene, a negative regulator of HbF, the second affects the expression of the MYB gene and the third determinants are miRNAs miR15a and 16-1 that negatively affect MYB expression. The minor allele at the BCL11A Ixus is found at increased frequencies in ?-thalassemia intermedia patients in which the attenuated phenotype is dependent on the increased output of HbF. In humans families, defects in KLF1 cause HPFH by reducing the expression of BCL11 A, hence establishing the hierarchy relationship KLF1
Genetic modifier factors of ß-thalassemia [Modificatori genetici della ß-talassemia]
MOI, PAOLO;
2011-01-01
Abstract
Recent genome wide association studies (GWAS) have identified several chromosomal loci responsible for the regulation of fetal hemoglobin (HbF) that are associated with the hereditary persistence of HbF (HPFH) in the adult life. Major new loci lie on chromosome 2,6 and 13. The first locus maps on the BCL11A gene, a negative regulator of HbF, the second affects the expression of the MYB gene and the third determinants are miRNAs miR15a and 16-1 that negatively affect MYB expression. The minor allele at the BCL11A Ixus is found at increased frequencies in ?-thalassemia intermedia patients in which the attenuated phenotype is dependent on the increased output of HbF. In humans families, defects in KLF1 cause HPFH by reducing the expression of BCL11 A, hence establishing the hierarchy relationship KLF1
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