Oral Presentation Indian Ocean Rim Laboratory Haematology Congress 2014

Hereditary persistence of fetal haemoglobin BCL11A single nucleotide polymorphism (SNP) genotyping study (#26)

Bradley Conway 1 2 , Jill Finlayson 1 2 , Christopher Newbound 3 , Reza Ghassemifar 1 2
  1. Department of Haematology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands, WA, Australia
  2. School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA, Australia
  3. Department of Diagnostic Genomics, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands, WA, Australia

Background

Hereditary persistence of fetal haemoglobin (HPFH) describes a range of disorders with a genetically determined persistence of fetal haemoglobin (HbF) production into adult life, in the absence of any other haemoglobin disorder. HbF levels are also a major ameliorating factor in the severity of β-globin disorders. BCL11A is a transcriptional repressor that inhibits adult stage HbF expression. The single nucleotide polymorphisms (SNPs) rs766432, rs1186868, rs4671393 and rs7557939 within the BCL11A gene have been shown to be associated with elevated HbF levels.

Methods

An assay was developed to test the above mentioned SNPs using commercially available TaqMan® PCR probe sets. The SNPs were validated by Sanger sequencing on representative samples.

Results

69 samples with HbF levels between 0.3-26.3% were identified in the departmental database, and genomic DNA was analysed for the existence of the above mentioned BCL11A SNPs. The results of the TaqMan® PCR analysis revealed the occurrence of all the genotypes for each of the SNPs of interest.

Conclusion

The TaqMan® PCR SNP genotyping assays for SNPs rs766432, rs11886868, rs4671393 and rs7557939 may be a useful diagnostic tool for the evaluation of elevated levels of HbF.