Concordance of a point mutation 5' to the (G)γ globin gene with (G)γβ+ hereditary persistence of fetal hemoglobin in the black population

F. S. Collins, C. D. Boehm, P. G. Waber, C. J. Stoeckert, S. M. Weissman, B. G. Forget, Haig Kazazian

Research output: Contribution to journalArticle

Abstract

Hereditary persistence of fetal hemoglobin (HPFH) is a genetically heterogeneous and clinically benign condition characterized by persistent expression of fetal hemoglobin (Hb F) into adulthood. In the (G)γβ+ type, no major deletions in the globin gene cluster occur; adult heterozygotes produce approximately 20% Hb F, which results from overproduction of (G)γ chains, with no apparent increase in production from the adjacent (A)γ gene. We have recently described a point mutation 202 base pairs 5' to the cap site of the (G)γ gene in an individual with (G)γβ+ HPFH. This mutation abolishes a normal ApaI restriction endonuclease site, and thus can be detected by blotting of genomic DNA. We present here further data on the ApaI mutation: (1) It occurs in six of seven families with (G)γβ+ HPFH. (2) In three families, detailed haplotype analysis using 11 polymorphic restriction sites in the β globin cluster has been done. The two that carry the missing ApaI site are identical but the third, which has a normal ApaI pattern, differs from the other two in at least two sites, one of which is a new polymorphic Nco I site between the δ and β globin genes. This suggests the possibility of a different HPFH mutation in the third family. (3) The haplotype of the (G)γβ+ HPFH chromosome carrying the ApaI mutation is different from that of 108 β(A) chromosomes of black individuals that have been tested. (4) The (G)γ ApaI site is normal in 61 β(A) and 109 β(S) alleles from non-HPFH black individuals, including 22 who share the same haplotype for the intragenic (G)γ, (A)γ HindIII polymorphisms. These data add support to the possibility that the -202 mutation is actually causative of the (G)γβ+ HPFH phenotype.

Original languageEnglish (US)
Pages (from-to)1292-1296
Number of pages5
JournalBlood
Volume64
Issue number6
StatePublished - 1984
Externally publishedYes

Fingerprint

Fetal Hemoglobin
Globins
Point Mutation
Genes
Population
Mutation
Haplotypes
Chromosomes
DNA Restriction Enzymes
Polymorphism
Heterozygote
Multigene Family
Base Pairing
Alleles
Phenotype
DNA

ASJC Scopus subject areas

  • Hematology

Cite this

Collins, F. S., Boehm, C. D., Waber, P. G., Stoeckert, C. J., Weissman, S. M., Forget, B. G., & Kazazian, H. (1984). Concordance of a point mutation 5' to the (G)γ globin gene with (G)γβ+ hereditary persistence of fetal hemoglobin in the black population. Blood, 64(6), 1292-1296.

Concordance of a point mutation 5' to the (G)γ globin gene with (G)γβ+ hereditary persistence of fetal hemoglobin in the black population. / Collins, F. S.; Boehm, C. D.; Waber, P. G.; Stoeckert, C. J.; Weissman, S. M.; Forget, B. G.; Kazazian, Haig.

In: Blood, Vol. 64, No. 6, 1984, p. 1292-1296.

Research output: Contribution to journalArticle

Collins, FS, Boehm, CD, Waber, PG, Stoeckert, CJ, Weissman, SM, Forget, BG & Kazazian, H 1984, 'Concordance of a point mutation 5' to the (G)γ globin gene with (G)γβ+ hereditary persistence of fetal hemoglobin in the black population', Blood, vol. 64, no. 6, pp. 1292-1296.
Collins FS, Boehm CD, Waber PG, Stoeckert CJ, Weissman SM, Forget BG et al. Concordance of a point mutation 5' to the (G)γ globin gene with (G)γβ+ hereditary persistence of fetal hemoglobin in the black population. Blood. 1984;64(6):1292-1296.
Collins, F. S. ; Boehm, C. D. ; Waber, P. G. ; Stoeckert, C. J. ; Weissman, S. M. ; Forget, B. G. ; Kazazian, Haig. / Concordance of a point mutation 5' to the (G)γ globin gene with (G)γβ+ hereditary persistence of fetal hemoglobin in the black population. In: Blood. 1984 ; Vol. 64, No. 6. pp. 1292-1296.
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abstract = "Hereditary persistence of fetal hemoglobin (HPFH) is a genetically heterogeneous and clinically benign condition characterized by persistent expression of fetal hemoglobin (Hb F) into adulthood. In the (G)γβ+ type, no major deletions in the globin gene cluster occur; adult heterozygotes produce approximately 20{\%} Hb F, which results from overproduction of (G)γ chains, with no apparent increase in production from the adjacent (A)γ gene. We have recently described a point mutation 202 base pairs 5' to the cap site of the (G)γ gene in an individual with (G)γβ+ HPFH. This mutation abolishes a normal ApaI restriction endonuclease site, and thus can be detected by blotting of genomic DNA. We present here further data on the ApaI mutation: (1) It occurs in six of seven families with (G)γβ+ HPFH. (2) In three families, detailed haplotype analysis using 11 polymorphic restriction sites in the β globin cluster has been done. The two that carry the missing ApaI site are identical but the third, which has a normal ApaI pattern, differs from the other two in at least two sites, one of which is a new polymorphic Nco I site between the δ and β globin genes. This suggests the possibility of a different HPFH mutation in the third family. (3) The haplotype of the (G)γβ+ HPFH chromosome carrying the ApaI mutation is different from that of 108 β(A) chromosomes of black individuals that have been tested. (4) The (G)γ ApaI site is normal in 61 β(A) and 109 β(S) alleles from non-HPFH black individuals, including 22 who share the same haplotype for the intragenic (G)γ, (A)γ HindIII polymorphisms. These data add support to the possibility that the -202 mutation is actually causative of the (G)γβ+ HPFH phenotype.",
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AU - Collins, F. S.

AU - Boehm, C. D.

AU - Waber, P. G.

AU - Stoeckert, C. J.

AU - Weissman, S. M.

AU - Forget, B. G.

AU - Kazazian, Haig

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N2 - Hereditary persistence of fetal hemoglobin (HPFH) is a genetically heterogeneous and clinically benign condition characterized by persistent expression of fetal hemoglobin (Hb F) into adulthood. In the (G)γβ+ type, no major deletions in the globin gene cluster occur; adult heterozygotes produce approximately 20% Hb F, which results from overproduction of (G)γ chains, with no apparent increase in production from the adjacent (A)γ gene. We have recently described a point mutation 202 base pairs 5' to the cap site of the (G)γ gene in an individual with (G)γβ+ HPFH. This mutation abolishes a normal ApaI restriction endonuclease site, and thus can be detected by blotting of genomic DNA. We present here further data on the ApaI mutation: (1) It occurs in six of seven families with (G)γβ+ HPFH. (2) In three families, detailed haplotype analysis using 11 polymorphic restriction sites in the β globin cluster has been done. The two that carry the missing ApaI site are identical but the third, which has a normal ApaI pattern, differs from the other two in at least two sites, one of which is a new polymorphic Nco I site between the δ and β globin genes. This suggests the possibility of a different HPFH mutation in the third family. (3) The haplotype of the (G)γβ+ HPFH chromosome carrying the ApaI mutation is different from that of 108 β(A) chromosomes of black individuals that have been tested. (4) The (G)γ ApaI site is normal in 61 β(A) and 109 β(S) alleles from non-HPFH black individuals, including 22 who share the same haplotype for the intragenic (G)γ, (A)γ HindIII polymorphisms. These data add support to the possibility that the -202 mutation is actually causative of the (G)γβ+ HPFH phenotype.

AB - Hereditary persistence of fetal hemoglobin (HPFH) is a genetically heterogeneous and clinically benign condition characterized by persistent expression of fetal hemoglobin (Hb F) into adulthood. In the (G)γβ+ type, no major deletions in the globin gene cluster occur; adult heterozygotes produce approximately 20% Hb F, which results from overproduction of (G)γ chains, with no apparent increase in production from the adjacent (A)γ gene. We have recently described a point mutation 202 base pairs 5' to the cap site of the (G)γ gene in an individual with (G)γβ+ HPFH. This mutation abolishes a normal ApaI restriction endonuclease site, and thus can be detected by blotting of genomic DNA. We present here further data on the ApaI mutation: (1) It occurs in six of seven families with (G)γβ+ HPFH. (2) In three families, detailed haplotype analysis using 11 polymorphic restriction sites in the β globin cluster has been done. The two that carry the missing ApaI site are identical but the third, which has a normal ApaI pattern, differs from the other two in at least two sites, one of which is a new polymorphic Nco I site between the δ and β globin genes. This suggests the possibility of a different HPFH mutation in the third family. (3) The haplotype of the (G)γβ+ HPFH chromosome carrying the ApaI mutation is different from that of 108 β(A) chromosomes of black individuals that have been tested. (4) The (G)γ ApaI site is normal in 61 β(A) and 109 β(S) alleles from non-HPFH black individuals, including 22 who share the same haplotype for the intragenic (G)γ, (A)γ HindIII polymorphisms. These data add support to the possibility that the -202 mutation is actually causative of the (G)γβ+ HPFH phenotype.

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