Haplotype analysis andAγ gene polymorphism associated with the Brazilian type of hereditary persistence of fetal hemoglobin
✍ Scribed by Bordin, Silvana; Martins, Juliana T.; Gonçalves, Marilda S.; Melo, Mônica B.; Saad, Sara T. O.; Costa, Fernando F.
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 186 KB
- Volume
- 58
- Category
- Article
- ISSN
- 0361-8609
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✦ Synopsis
We have identified three unrelated individuals and three members of a family with the non-deletion form of A ␥-hereditary persistence of fetal hemoglobin (HPFH). Molecular analysis showed that each individual is a heterozygote for a previously described -195 A ␥ (C→G) mutation. The -globin gene cluster was studied using the polymerase chain reaction and related techniques. Haplotyping using nine restriction sites identified two closely related chromosomes with the -195 A ␥ mutation, differing only in a single site 3 to the -globin gene. Further analysis of -globin framework indicated that the HPFH allele segregates with haplotype V, according to Orkin's classification. The second haplotype probably originated by a point mutation or DNA rearrangement of a pre-existing -195 A ␥ chromosome. We also determined the sequences from -622 to +55 bp upstream to the A ␥ gene and part of the A ␥ IVS-2. We found four polymorphisms associated to the -195 A ␥ promoter region. All -195 A ␥ chromosomes had a G at positions -588 and +25 relative to the A ␥ gene. One individual was also homozygous for polymorphisms at -398 (G→A), and another at -369 (C→G). Cloning and sequencing of the polymorphic patterns of the 3 region of A ␥ IVS-2 showed that the mutated allele is linked to -globin chromosome B. Some correlations between chromosome characteristics and A ␥ point mutations were also observed. Am.