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 Blood, 15 August 2005, Vol. 106, No. 4, pp. 1466-1472.
Prepublished online as a Blood First Edition Paper on April 26, 2005; DOI 10.1182/blood-2005-03-0948.

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RED CELLS

A newly discovered human {alpha}-globin gene

Sung-Ho Goh, Y. Terry Lee, Natarajan V. Bhanu, Margaret C. Cam, Richard Desper, Brian M. Martin, Ramy Moharram, Robert B. Gherman, and Jeffery L. Miller

From the Molecular Medicine Branch and the Microarray Core Facility, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH); National Center for Biotechnology Information (NCBI), NIH; Laboratory of Neurotoxicology, National Institute of Mental Health, NIH; and National Naval Hospital, Bethesda, MD.

A previously undefined transcript with significant homology to the pseudo-{alpha}2 region of the {alpha}-globin locus on human chromosome 16 was detected as part of an effort to better define the transcriptional profiles of human reticulocytes. Cloning and sequencing of that transcript (GenBank AY698022; named µ-globin) revealed an insert with a 423-nucleotide open reading frame. BLASTP and ClustalW and phylogenetic analyses of the predicted protein demonstrated a high level of homology with the avian {alpha}-D globin. In addition, the heme- and globin-binding amino acids of µ-globin and avian {alpha}-D globin are largely conserved. Using quantitative real-time polymerase chain reaction (PCR), µ-globin was detected at a level of approximately 0.1% that measured for {alpha}-globin in erythroid tissues. Erythroid-specific expression was detected by Northern blot analysis, and maximal expression during the erythroblast terminal differentiation was also detected. Despite this highly regulated pattern of µ-globin gene transcription, µ-globin protein was not detected by mass spectrometry. These results suggest the human genome encodes a previously unrecognized globin member of the avian {alpha}-D family that is transcribed in a highly regulated pattern in erythroid cells. (Blood. 2005;106:1466-1472)


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