Changes in the G gamma- and A gamma-globin mRNA components of fetal hemoglobin during human development

H Bard1, K G Peri, C Gagnon

  • 1Service of Neonatalogy, Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada. bardh@ere.umontreal.ca

Insights

Fetal hemoglobin (HbF) shows developmental changes in gamma-globin mRNA proportions. High (G)gamma-globin mRNA levels in adults are linked to a specific gene promoter variation.

Area of Science:

  • Molecular Biology
  • Hematology
  • Genetics

Background:

  • Hemoglobin F (HbF) is crucial during fetal development, composed of (G)gamma- and (A)gamma-globin chains.
  • Understanding the developmental shifts in HbF composition is vital for diagnosing and managing certain anemias and blood disorders.

Purpose of the Study:

  • To investigate the postnatal developmental changes in (G)gamma- and (A)gamma-globin messenger RNA (mRNA) levels of HbF.
  • To explore the association between gamma-globin mRNA proportions and the -158 (C-->T) polymorphism in adults.

Main Methods:

  • Blood samples were collected from preterm infants (< or = 33 weeks gestation), term-born infants, and adults.
  • Quantitative analysis of (G)gamma- and (A)gamma-globin mRNA levels was performed.
  • Correlation analysis was conducted between mRNA levels and the -158 (C-->T) promoter polymorphism in adult samples.

Main Results:

  • (G)gamma-globin mRNA constituted approximately 66% of total gamma-globin mRNA until 44 weeks postconceptual age.
  • A significant shift in the proportions of (G)gamma- and (A)gamma-globin mRNA occurred after 44 weeks.
  • Adults exhibited a wide range of (G)gamma-globin mRNA levels (20-74%), with higher proportions associated with the -158 (C-->T) polymorphism (gene frequency 0.32).

Conclusions:

  • Postnatal development involves significant changes in the relative expression of (G)gamma- and (A)gamma-globin genes.
  • The -158 (C-->T) promoter polymorphism is a key genetic factor influencing HbF composition in adults.

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