Dear Sir,
The original article titled “Multi centric origin of Hb D-Punjab [β121(GH4)Glu→Gln, GAA>CAA]” recently published by Yavarian et al. (1) describes the β-globin gene cluster haplotypes linked with Hb D-Punjab observed in Southern Iran (Hormozgan and Fars provinces), The Netherlands and Belgium.
Although the above authors cited that a novel β-globin gene cluster haplotype [– + – – + + +], reported from Turkey (Citation2), was linked with Hb D-Punjab [β121(GH4)Glu→Gln, GAA>CAA] in their original article, I would like to draw your attention to another novel haplotype, namely [– – + – + + +], also reported from Turkey (Citation3). Haplotype analysis was done by polymerase chain reaction (PCR)-based restriction enzyme digestion for the β-globin gene cluster at the following polymorphic restriction sites: HincII 5′to ε, HindIII 5′to Gγ, HindIII 5′ to Aγ, HincII in ψβ, AvaII in β and HinfI 3′ to β.
While considering the situation in Denizli Province in the Aegean region of Turkey, most unrelated Hb D-Punjab families are also linked with the haplotype structure of [+ – – – – + +], as observed in other populations. Normal population data show us that the Hb D-Punjab mutation developed on the most common normal population haplotype of [+ – – – – + +] with a frequency of 28.6% (Citation4). According to Bahadir et al. (Citation4), other normal population haplotypes are [+ – – – – + –] (17.2%), [– + – + + + +] (9.8%), [+ – – – – – +] (8.3%), [– + – + + – +] (6.8%), [– + + – + + +] (6.4%), etc. In Turkey, we observed the haplotypes of [+ – – – – + +], [– + – – + + +], [– + + – + + +], [– – + – + + +] in linkage with the Hb D-Punjab mutation (Citation3,Citation5). As most haplotypes of the Hb D-Punjab mutation in Turkey is linked with haplotype [+ – – – – + +], this mutation is mostly developed in the genetic background of the normal population. The other haplotypes could have been introduced into the gene pool. Unfortunately, due to the lack of data, except Thai samples (Citation6), in connection with Asian samples cannot be compared at the moment.
I also agree with the opinion of the authors of the original article (Citation1) that the higher mutation rate at codon 121 of the β-globin gene could explain the presence of Hb D-Punjab in different populations, as well as population movements and gene conversion events.
Short Comment in Response to the Above Letter
Dear Sir,
Yavarian et al. are grateful to their colleague Dr. Erol Ö. Atalay (Professor of Biophysics, Department of Biophysics, Medical Faculty, Pamukkale University, Denizli, Turkey) for the additional data. We are pleased to read that he also shares the hypothesis that the Hb D-Punjab [β121 (GH4)Glu→Gln, GAA>CAA] mutation occurs in many populations, on different haplotypes and often on the most commonly encountered, indicating a combination of gene flow, founder effect and an increased mutation rate at position β121.
REFERENCES
- Yavarian M, Karimi M, Paran F, Neven C, Harteveld CL, Giordano PC. Multi centric origin of Hb D‐Punjab [β121(GH4)Glu→Gln, GAA>CAA]. Hemoglobin. 2009;33(6):399–405.
- Atalay EÖ, Atalay A, Üstel E, Genetic origin of Hb D-Los Angeles [β121(GH4)Glu→Gln, GAA>CAA] according to the β-globin gene cluster haplotypes. Hemoglobin. 2007;31(3):387–391.
- Bahadir A, Koseler A, Atalay A, Hb D-Los Angeles [β121(GH4)Glu→Gln] and Hb Beograd [β121(GH4)Glu→Val]: implications for their laboratory diagnosis and genetic origins. Turk J Hematol. 2009;26(1):17–20.
- Bahadir A, Ozturk O, Atalay A, Atalay EO. β Globin gene cluster haplotypes of the β thalassemia mutations observed in the Denizli province of Turkey. Turk J Hematol. 2009;26(3):129–137.
- Ozturk O, Atalay A, Koseler A, β Globin gene cluster haplotypes of abnormal hemoglobins observed in Turkey. Turk J Hematol. 2007;24(4):146–154.
- Fuchaoren S, Changtrakun Y, Surapot S, Fucharoen G, Sanchaisuriya K. Molecular characterization of Hb D-Punjab [β121(GH4)Glu→Gln] in Thailand. Hemoglobin. 2002;26(3):261–269.