The 5′ Regulatory Region of the Human Fetal Globin Genes is a Gene Conversion Hotspot

Abstract

The human fetal globin genes consist of the first mammalian genomic loci for which gene conversion was reported. To date, 14 gene conversions have been described in the human ^Gγ- and ^Aγ-globin genes, the vast majority of which are restricted to the coding sequences. Here, we provide evidence for three new gene conversion events in the 5′ regulatory region of the human fetal globin genes, identified during a large genetic screening effort in adult individuals with high fetal hemoglobin (Hb) levels. The sequence variations, resulting from these conversion events, are transcriptionally silent polymorphisms that do not contribute to increased fetal Hb levels. Our results suggest that the 5′ regulatory region of the human fetal globin genes is a gene conversion hotspot that prevent globin gene promoter sequence diversification, further underlining the need for two functional fetal globin genes in fetal erythropoiesis.

Keywords:

• Gene conversion
• Fetal globin genes
• Fetal hemoglobin (Hb)
• ^Gγ-Globin gene
• ^Aγ-Globin gene
• Sequence homogenization
• Sequence variations