Certain mutations observed in the 5’ sequences of the^Gγ-and^Aγ-globin genes of β^Schromosomes are specific for chromosomes with major haplotypes

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.