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7 - Hemoglobins of the Embryo, Fetus, and Adult

from SECTION ONE - THE MOLECULAR, CELLULAR, AND GENETIC BASIS OF HEMOGLOBIN DISORDERS

Published online by Cambridge University Press:  03 May 2010

Martin H. Steinberg ,
Bernard G. Forget ,
Douglas R. Higgs  and
David J. Weatherall
By
Martin H. Steinberg  and
Ronald L. Nagel
Martin H. Steinberg
Affiliation:
Boston University
Bernard G. Forget
Affiliation:
Yale University, Connecticut
Douglas R. Higgs
Affiliation:
MRC Institute of Molecular Medicine, University of Oxford
David J. Weatherall
Affiliation:
Albert Einstein College of Medicine, New York
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Summary

INTRODUCTION

During development, humans express six different hemoglobin types, the products of eight different globin genes (Fig. 3.1, Chapter 3). Hb Gower I (ς2ε2), Gower II (α2ε2), and Portland (ς2γ2) are found in the embryo, fetal hemoglobin (HbF; α2γ2) is present mainly in the fetus but also in the embryo and adult, whereas HbA (α2β2) and HbA2 (α2δ2) are seen primarily in adults. All hemoglobins undergo posttranslational modifications forming minor hemoglobins. Globin genes are discussed in Chapter 3, hemoglobin switching in Chapter 5, and the structure and function of hemoglobin in Chapter 6 and. In this chapter we discuss the clinical and physiological attributes of HbF, HbA2, embryonic hemoglobins, and their posttranslational modifications.

HEMOGLOBIN F

The observation that hemoglobin in newborns' erythrocytes was resistant to alkaline denaturation provided the first suggestion that a hemoglobin existed that differed from normal HbA.

Structure of the γ-Globin Genes and γ-Globin

γ-Globin chains differ from β-globin chains in either 39 or 40 amino acid residues, depending on whether a glycine or alanine residue is present at γ136. γ-Globin is the product of two nearly identical γ-globin genes. A glycine codon is present in the 5′ or Gγ gene (HBG2) and an alanine codon characterizes the 3′, or Aγ gene (HBG1). Also, a common polymorphism is found in the Aγ gene, where threonine (AγT) replaces isoleucine (AγI) at codon γ75 (HbF-Sardinia). This striking similarity in protein sequence and structure of the γ-globin genes reflect their concerted evolution from gene duplication and gene conversion.

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Type
Chapter
Information
Disorders of Hemoglobin
Genetics, Pathophysiology, and Clinical Management
 , pp. 119 - 136
Publisher: Cambridge University Press
Print publication year: 2009

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