Hemoglobins of the Embryo, Fetus, and Adult

Steinberg, Martin H.; Nagel, Ronald L.

doi:10.1017/cbo9780511596582.011

Cited by 14 publications

(8 citation statements)

References 82 publications

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“…We believe that the HBS1L‐MYB locus on chromosome 6 affects HbA 2 levels predominantly through the kinetics of erythropoiesis. Our results suggest that FC contain more HbA 2 than non–F erythrocytes, supporting the notion that the HbA 2 content and Hb composition of erythroid cells change during maturation (Steinberg & Nagel, ). It seems that the second locus on chromosome 11p affects HBD expression via competitive interaction with HBB, simulating a mild β‐thalassaemia phenotype consistent with the proposed effect of rare KLF1 variants on HbA 2 expression (Perseu et al , ).…”

Section: Resultssupporting

confidence: 88%

“…It is presently not known how HbA 2 (and δ‐globin chain) expression changes during adult erythropoiesis, but it has been suggested that δ‐globin chain synthesis declines as maturation in erythroid progenitors progresses (Steinberg & Nagel, ). As HBD is located between the two γ ( HBG1, HBG2 ) and β ( HBB ) genes, one can surmise that its expression during erythroid maturation closely follows that of γ, but precedes that of β, and peaks before progenitors reach full maturity.…”

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confidence: 99%

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HbA₂ levels in normal adults are influenced by two distinct genetic mechanisms

et al. 2012

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SummaryUsing a genome-wide association study, we found that common inter-individual differences in haemoglobin A 2 (HbA 2 , a 2 d 2 ) levels are largely governed by genetic factors (42% of variability). The influence of age (1%) and sex (4%) was small. HbA 2 levels were influenced by two loci: the HBS1L-MYB locus on chromosome 6q, which has been shown to have pleiotropic effects on other haematological traits; and a second locus surrounding HBB, the gene encoding b-globin. Our results suggest that HbA 2 levels in adults are influenced by two different biological processes: one via kinetics of erythropoiesis, and the other, via competition between HBB and HBD activity.

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Section: Resultssupporting

confidence: 88%

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confidence: 99%

HbA₂ levels in normal adults are influenced by two distinct genetic mechanisms

et al. 2012

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“…17 Although erythroid precursors of normal adults express HBG at a low level, 18 stress erythropoiesis is associated with increased HbF. [19][20][21] A stochastic model posits that the increase in HbF is the result of recruitment of erythroid progenitor cells that prematurely undergo terminal differentiation and are committed to producing ␥-globin.…”

Section: Genetic Basis Of Hbf Regulation Globin Gene Switchingmentioning

confidence: 99%

Fetal hemoglobin in sickle cell anemia

Akinsheye

Alsultan

Solovieff

et al. 2011

Blood

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432

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Fetal hemoglobin (HbF) is the major genetic modulator of the hematologic and clinical features of sickle cell disease, an effect mediated by its exclusion from the sickle hemoglobin polymer. Fetal hemoglobin genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Some patients with sickle cell disease have exceptionally high levels of HbF that are associated with the Senegal and Saudi-Indian haplotype of the HBB-like gene cluster; some patients with different haplotypes can have similarly high HbF. In these patients, high HbF is associated with generally milder but not asymptomatic disease. Studying these persons might provide additional insights into HbF gene regulation. HbF appears to benefit some complications of disease more than others. This might be related to the premature destruction of erythrocytes that do not contain HbF, even though the total HbF concentration is high. Recent insights into HbF regulation have spurred new efforts to induce high HbF levels in sickle cell disease beyond those achievable with the current limited repertory of HbF inducers.

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“…This work was done prior to the discovery of the association of BCL11A with HBG expression. SNPs in genes within the 6q and 8q linkage peaks, and also the ARG2 , FLT1 , HAO2 , and NOS1 genes were associated with the HbF response to hydroxyurea [104].…”

Section: Hbfmentioning

confidence: 99%

Genetic modifiers of sickle cell disease

2012

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Sickle cell anemia is associated with unusual clinical heterogeneity for a Mendelian disorder. Fetal hemoglobin concentration and coincident α thalassemia, both which directly affect the sickle erythrocyte, are the major modulators of the phenotype of disease. Understanding the genetics underlying the heritable subphenotypes of sickle cell anemia would be prognostically useful, could inform personalized therapeutics, and might help the discovery of new “druggable” pathophysiologic targets. Genotype‐phenotype association studies have been used to identify novel genetic modifiers. In the future, whole genome sequencing with its promise of discovering hitherto unsuspected variants could add to our understanding of the genetic modifiers of this disease. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.

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Hemoglobins of the Embryo, Fetus, and Adult

Cited by 14 publications

References 82 publications

HbA₂ levels in normal adults are influenced by two distinct genetic mechanisms

HbA₂ levels in normal adults are influenced by two distinct genetic mechanisms

Fetal hemoglobin in sickle cell anemia

Genetic modifiers of sickle cell disease

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Hemoglobins of the Embryo, Fetus, and Adult

Cited by 14 publications

References 82 publications

HbA2 levels in normal adults are influenced by two distinct genetic mechanisms

HbA2 levels in normal adults are influenced by two distinct genetic mechanisms

Fetal hemoglobin in sickle cell anemia

Genetic modifiers of sickle cell disease

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Product

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HbA₂ levels in normal adults are influenced by two distinct genetic mechanisms

HbA₂ levels in normal adults are influenced by two distinct genetic mechanisms