title: Characterization of Deletions of the HBA and HBB Loci by Array Comparative Genomic Hybridization.
abstract: Thalassemia is among the most common genetic diseases worldwide. α-Thalassemia is usually caused by deletion of one or more of the duplicated HBA genes on chromosome 16. In contrast, most β-thalassemia results from point mutations that decrease or eliminate expression of the HBB gene on chromosome 11. Deletions within the HBB locus result in thalassemia or hereditary persistence of fetal Hb. Although routine diagnostic testing cannot distinguish thalassemia deletions from point mutations, deletional hereditary persistence of fetal Hb is notable for having an elevated HbF level with a normal mean corpuscular volume. A small number of deletions accounts for most α-thalassemias; in contrast, there are no predominant HBB deletions causing β-thalassemia. To facilitate the identification and characterization of deletions of the HBA and HBB globin loci, we performed array-based comparative genomic hybridization using a custom oligonucleotide microarray. We accurately mapped the breakpoints of known and previously uncharacterized HBB deletions defining previously uncharacterized deletion breakpoints by PCR amplification and sequencing. The array also successfully identified the common HBA deletions --(SEA) and --(FIL). In summary, comparative genomic hybridization can be used to characterize deletions of the HBA and HBB loci, allowing high-resolution characterization of novel deletions that are not readily detected by PCR-based methods.
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington. Electronic address: dsabath@uw.edu.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Sabath
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bender
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Vijay G
authors.initials: VG
authors.lastname: Sankaran
authors.affiliation: Departments of Pediatrics and Genetics, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Esther
authors.initials: E
authors.lastname: Vamos
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Alex
authors.initials: A
authors.lastname: Kentsis
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington.
authors.forename: Hye-Son
authors.initials: HS
authors.lastname: Yi
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington. Electronic address: hagreisman@gmail.com.
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Greisman
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D017353:Gene Deletion; D006441:Hemoglobin A / Q000235:genetics*; D006454:Hemoglobins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D016133:Polymerase Chain Reaction; D055542:alpha-Globins / Q000235:genetics; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics*; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D006454:Hemoglobins; D055542:alpha-Globins; D055544:beta-Globins; D006441:Hemoglobin A; C020622:hemoglobin B