PMID- 16519704
OWN - NLM
STAT- MEDLINE
DCOM- 20060505
LR  - 20081121
IS  - 0902-4441 (Print)
IS  - 0902-4441 (Linking)
VI  - 76
IP  - 4
DP  - 2006 Apr
TI  - Genotypic heterogeneity and correlation to intergenic haplotype within high HbF 
      beta-thalassemia intermedia.
PG  - 322-30
AB  - OBJECTIVES: A molecular study was carried out of beta-thalassemia intermedia 
      patients, compound heterozygotes for mutations usually found in beta-thalassemia 
      major, with high levels of HbF in the absence of hereditary persistence of fetal 
      hemoglobin (HPFH) syndrome. Our objective was to locate cis-DNA structures, DNA 
      haplotypes, motifs, or polymorphisms that may correlate with the presence of high 
      HbF. METHODS: Allele-specific oligonucleotide (ASO) hybridization was used for 
      the detection of mutations and restriction fragment length polymorphism (RFLP) 
      analysis and automated sequencing for motifs, haplotypes, and polymorphisms. 
      Southern blot was used for investigating alpha-thalassemia and/or alpha- or 
      gamma-globin genes triplications. RNA extracted from burst forming unit-erythroid 
      (BFU-e) colonies of peripheral blood mononuclear cell cultures was used in 
      reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate 
      intergenic transcription. RESULTS: We established that (i) the combination: T 
      haplotype of the Agamma-delta-globin intergenic region, the motif (TA)9N10(TA)10 
      in the HS2 site of locus control region (LCR), and TAG pre-Ggamma haplotype is 
      sufficient but not necessary for high HbF, (ii) the genetic determinant(s) for 
      high HbF involves an element associated with this combination and must be present 
      in the specific R haplotype occurring in beta-thalassemia intermedia and (iii) 
      the genetic determinant(s) for high HbF does not involve the abolition of 
      intergenic transcription in the Agamma-delta-globin intergenic region. 
      CONCLUSIONS: The genetic determinant(s) of high HbF in the absence of HPFH is 
      linked to intergenic haplotype T and does not disrupt intergenic transcription.
FAU - Papachatzopoulou, Adamantia
AU  - Papachatzopoulou A
AD  - Department of General Biology, Medical Faculty, University of Patras, Athens, 
      Greece.
FAU - Kourakli, Alexandra
AU  - Kourakli A
FAU - Makropoulou, Panagiota
AU  - Makropoulou P
FAU - Kakagianne, Theodora
AU  - Kakagianne T
FAU - Sgourou, Argyro
AU  - Sgourou A
FAU - Papadakis, Manousos
AU  - Papadakis M
FAU - Athanassiadou, Aglaia
AU  - Athanassiadou A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Haematol
JT  - European journal of haematology
JID - 8703985
RN  - 0 (DNA, Intergenic)
RN  - 9004-22-2 (Globins)
RN  - 9034-63-3 (Fetal Hemoglobin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - DNA, Intergenic/*genetics
MH  - Female
MH  - Fetal Hemoglobin/*analysis/genetics
MH  - Genetic Variation/*genetics
MH  - Globins/*genetics
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Quantitative Trait Loci/genetics
MH  - alpha-Thalassemia/blood/genetics
MH  - beta-Thalassemia/*blood/*genetics
EDAT- 2006/03/08 09:00
MHDA- 2006/05/06 09:00
CRDT- 2006/03/08 09:00
PHST- 2006/03/08 09:00 [pubmed]
PHST- 2006/05/06 09:00 [medline]
PHST- 2006/03/08 09:00 [entrez]
AID - EJH618 [pii]
AID - 10.1111/j.1600-0609.2005.00618.x [doi]
PST - ppublish
SO  - Eur J Haematol. 2006 Apr;76(4):322-30. doi: 10.1111/j.1600-0609.2005.00618.x.