Certain Mutations Observed in the 5´ Sequences of the ^Gγ- and ^Aγ-Globin Genes of β^s Chromosomes Are Specific for Chromosomes with Major Haplotypes

Abstract

In this paper we describe the distribution of some specific sequence differences in the 5’ flanking regions of the ^Aγ- and ^Gγ-globin genes from 100 Black adult and 57 newborn SS patients from the southeastern United States, from 76 individuals with AS, S-β-thal, SC, AC, or A-β-thal, and from 31 normal individuals. Haplotypes for all adult individuals have been previously determined using various restriction endonucleases. The DNA samples were amplified, dot blotted, and hybridized with ³²P-labeled specific oligonucleotide probes. All 134 chromosomes with haplotype 19 were positive for the G → T substitution at position -657 (^Aγ), while 132 were also positive for the C→G mutation at -369 (^Gγ). The three specific changes for the chromosome with haplotype 20 were found on all 54 chromosomes with this haplotype. The C→T mutation at -158 5’ to ^Gγ was present on all 41 chromosomes with haplotype 3, and on two chromosomes with a related atypical haplotype. Normal and β-thal chromosomes with each of these substitutions had the same 5’ subhaplotype as β^s haplotypes 19 or 20, respectively. The close relationship between the occurrence of specific mutations and the haplotype of β^s chromosomes makes the determination of these haplotypes with specific oligonucleotide probes attractive with respect to time and expense.

Spectrum of β thalassemia mutations and HbF levels in the heterozygous Moroccan population

“…Its possible role as modulator of expression of human globin genes [44] needs further investigation. This -369 A␥ polymorphism is commonly found in the G␥ gene [45], but its role in gene regulation has not yet been described. In the absence of experimental data on the regulatory function of the G␥ and A␥ polymorphisms per se or as linkage markers of HbF expression, one could speculate that the -369 A␥ polymorphism, in association with the reduction of ␤ gene transcription by the TATA box mutation [46], possibly creates an imbalance of transcription factors, favoring an HbF elevation under the mild erythropoietic stress caused by ␤ thalassemia heterozygous condition.…”

Temporal sequence of splenic dysfunction in sickle cell disease

“…All the SS patients were screened for the presence of a-thal-2 (À3.7 kb) deletion that is the commonest cause of a-thal trait in this community [20]. The b Sglobin gene cluster haplotypes were determined using allele-speci®c oligonucleotide hybridization to identify haplotype-speci®c mutations in the 5¢¯anking and IVS-II regions of the G c-and A c-globin genes as previously described [6,21].…”

Influence of α-Thalassemia on Cholelithiasis in SS Patients with Elevated Hb F

“…These mutations were specific for the SAI, Benin (Ben), or the Bantu (Ban) haplotypes. Details of the methodology have been previously described [17, 18]. The α-globin gene patterns were determined by screening for the –3.7 kb deletion using a modified Baysal and Huisman polymerase chain reaction (PCR) method [19].…”