Fetal hemoglobin levels in sickle cell disease and normal individuals are partially controlled by an X-linked gene located at Xp22.2

George J Dover, Kirby D. Smith, Y. C. Chang, S. Purvis, A. Mays, D. A. Meyers, C. Sheils, G. Serjeant

Research output: Contribution to journalArticle

Abstract

Fetal hemoglobin (Hb F) production in sickle cell (SS) disease and in normal individuals varies over a 20-fold range and is under genetic control. Previous studies suggested that variant Hb F levels might be controlled by genetic loci separate from the β-globin complex on chromosome 11. Using microscopic radial immunodiffusion and flow cytometric immunofluorescent assays to determine the percentage of F reticulocytes and F cells in SS and nonanemic individuals, we observed that F-cell levels were significantly higher in nonanemic females than males (mean ± SD, 3.8% ± 3.2% v 2.7% ± 2.3%). F-cell production as determined by F reticulocyte levels in SS females was also higher than in SS males (17% ± 10% v 13% ± 8%). We tested the hypothesis that F-cell production in both normal and anemic SS individuals was controlled by an X-linked locus with two alleles, high (H) and low (L). Using an algorithm to determine the 99.8% confidence interval of a normal distribution in nonanemic individuals, we estimated that males and females with at least one H allele had greater than 3.3% F cells. Comparisons of male-male or female-female SS sib pairs with discordant F reticulocyte levels distinguished two phenotypes in SS males (L, 12%) and three phenotypes in SS females (LL, 24%). Linkage analysis using polymorphic restriction sites along the X chromosome in eight SS and one AA family localized the F-cell production (FCP) locus to Xp22.2, with a maximum lod score (logarithm of odds of linkage v independent assortment) of 4.6 at a recombination fraction of 0.04.

Original languageEnglish (US)
Pages (from-to)816-824
Number of pages9
JournalBlood
Volume80
Issue number3
StatePublished - Aug 1 1992

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Fetal Hemoglobin
X-Linked Genes
Sickle Cell Anemia
Genes
Reticulocytes
Chromosomes
Globins
Normal distribution
Alleles
Lod Score
Phenotype
Assays
Chromosomes, Human, Pair 11
Genetic Loci
Immunodiffusion
Normal Distribution
X Chromosome
Genetic Recombination
Confidence Intervals

ASJC Scopus subject areas

  • Hematology

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Fetal hemoglobin levels in sickle cell disease and normal individuals are partially controlled by an X-linked gene located at Xp22.2. / Dover, George J; Smith, Kirby D.; Chang, Y. C.; Purvis, S.; Mays, A.; Meyers, D. A.; Sheils, C.; Serjeant, G.

In: Blood, Vol. 80, No. 3, 01.08.1992, p. 816-824.

Research output: Contribution to journalArticle

Dover, GJ, Smith, KD, Chang, YC, Purvis, S, Mays, A, Meyers, DA, Sheils, C & Serjeant, G 1992, 'Fetal hemoglobin levels in sickle cell disease and normal individuals are partially controlled by an X-linked gene located at Xp22.2', Blood, vol. 80, no. 3, pp. 816-824.
Dover, George J ; Smith, Kirby D. ; Chang, Y. C. ; Purvis, S. ; Mays, A. ; Meyers, D. A. ; Sheils, C. ; Serjeant, G. / Fetal hemoglobin levels in sickle cell disease and normal individuals are partially controlled by an X-linked gene located at Xp22.2. In: Blood. 1992 ; Vol. 80, No. 3. pp. 816-824.
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abstract = "Fetal hemoglobin (Hb F) production in sickle cell (SS) disease and in normal individuals varies over a 20-fold range and is under genetic control. Previous studies suggested that variant Hb F levels might be controlled by genetic loci separate from the β-globin complex on chromosome 11. Using microscopic radial immunodiffusion and flow cytometric immunofluorescent assays to determine the percentage of F reticulocytes and F cells in SS and nonanemic individuals, we observed that F-cell levels were significantly higher in nonanemic females than males (mean ± SD, 3.8{\%} ± 3.2{\%} v 2.7{\%} ± 2.3{\%}). F-cell production as determined by F reticulocyte levels in SS females was also higher than in SS males (17{\%} ± 10{\%} v 13{\%} ± 8{\%}). We tested the hypothesis that F-cell production in both normal and anemic SS individuals was controlled by an X-linked locus with two alleles, high (H) and low (L). Using an algorithm to determine the 99.8{\%} confidence interval of a normal distribution in nonanemic individuals, we estimated that males and females with at least one H allele had greater than 3.3{\%} F cells. Comparisons of male-male or female-female SS sib pairs with discordant F reticulocyte levels distinguished two phenotypes in SS males (L, 12{\%}) and three phenotypes in SS females (LL, 24{\%}). Linkage analysis using polymorphic restriction sites along the X chromosome in eight SS and one AA family localized the F-cell production (FCP) locus to Xp22.2, with a maximum lod score (logarithm of odds of linkage v independent assortment) of 4.6 at a recombination fraction of 0.04.",
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N2 - Fetal hemoglobin (Hb F) production in sickle cell (SS) disease and in normal individuals varies over a 20-fold range and is under genetic control. Previous studies suggested that variant Hb F levels might be controlled by genetic loci separate from the β-globin complex on chromosome 11. Using microscopic radial immunodiffusion and flow cytometric immunofluorescent assays to determine the percentage of F reticulocytes and F cells in SS and nonanemic individuals, we observed that F-cell levels were significantly higher in nonanemic females than males (mean ± SD, 3.8% ± 3.2% v 2.7% ± 2.3%). F-cell production as determined by F reticulocyte levels in SS females was also higher than in SS males (17% ± 10% v 13% ± 8%). We tested the hypothesis that F-cell production in both normal and anemic SS individuals was controlled by an X-linked locus with two alleles, high (H) and low (L). Using an algorithm to determine the 99.8% confidence interval of a normal distribution in nonanemic individuals, we estimated that males and females with at least one H allele had greater than 3.3% F cells. Comparisons of male-male or female-female SS sib pairs with discordant F reticulocyte levels distinguished two phenotypes in SS males (L, 12%) and three phenotypes in SS females (LL, 24%). Linkage analysis using polymorphic restriction sites along the X chromosome in eight SS and one AA family localized the F-cell production (FCP) locus to Xp22.2, with a maximum lod score (logarithm of odds of linkage v independent assortment) of 4.6 at a recombination fraction of 0.04.

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