Certain mutations observed in the 5' sequences of the G gamma- and A gamma-globin genes of beta S chromosomes 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 A gamma- and G gamma-globin genes from 100 Black adult and 57 newborn SS patients from the southeastern United States, from 76 individuals with AS, S-beta-thal, SC, AC, or A-beta-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 (A gamma), while 132 were also positive for the C----G mutation at -369 (G gamma). 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 G gamma was present on all 41 chromosomes with haplotype 3, and on two chromosomes with a related atypical haplotype. Normal and beta-thal chromosomes with each of these substitutions had the same 5' subhaplotype as beta S haplotypes 19 or 20, respectively. The close relationship between the occurrence of specific mutations and the haplotype of beta S chromosomes makes the determination of these haplotypes with specific oligonucleotide probes attractive with respect to time and expense.
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta.
A J
AJ
Dimovski
C
C
Oner
S
S
Agarwal
Y C
YC
Gu
L H
LH
Gu
F
F
Kutlar
K D
KD
Lanclos
T H
TH
Huisman
D000328:Adult; D000755:Anemia, Sickle Cell / Q000235:genetics; D001483:Base Sequence; D044383:Black People; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006445:Hemoglobin C Disease / Q000235:genetics; D006450:Hemoglobin SC Disease / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D012150:Polymorphism, Restriction Fragment Length; D013789:Thalassemia / Q000235:genetics
D015345:Oligonucleotide Probes; D005914:Globins