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- Title
Molecular Analysis of alpha globin gene mutations in BC Families.
- Authors
Lambert, Anne; Wong, Ann; Wadsworth, Louis D.; Au, Nicholas; MacGillivray, Ross
- Abstract
Introduction and Objective: Mutations in hemoglobin can lead to structural changes which hinder its ability to transport oxygen throughout the body and can lead to anemia. Hemoglobin in humans consists of four globin chains - the vast majority of these tetramers being made up of two alpha chains and two beta chains. The alpha globin gene is present at two loci on chromosome 16. These duplicated alpha globin genes have identical coding sequences and a high GC content which complicates their ability to be amplified separately via Polymerase Chain Reaction (PCR). This study aims to individually amplify α1 (HBA1) and α2 (HBA2) in order to sequence the genes to look for single nucleotide polymorphisms (SNPs) or deletions. Methods: Blood samples of patients that showed abnormalities in the alpha globin with HPLC analysis were obtained from B.C. Children's and Women's Hospital. The HBA1 and HBA2 genes were amplified separately using PCR. The resulting product was subjected to automated DNA sequence analysis. Results: PCR amplification with alpha globin primers produced an 880bp product for HBA2 and an 887bp product for HBA1. Further sequential analyses of the amplified product produced 2 cases of note: Alpha hemoglobin PCR on a patient presenting with mild microcytic anemia revealed that she has both -alpha 3.7 and -alpha 4.2 deletions. HPLC produced an unknown peak indicating the presence of a hemoglobin variant and sequencing revealed an Asp74His amino acid change. This combination has been described only once previously as a double heterozygote for Hb Q-Thailand and α+-thalassemia (-αQT/-α3.7). On routine screening for common alpha thalassemia deletions, a mother and son were found to have a deletion of 204bp in one allele of HBA2. Sequential analysis led to the discovery of the break points and the conclusion that exon 3 of HBA2 had been deleted. Conclusion: HBA1 and HBA2 can be amplified separately in order to locate a variety of SNPs or deletions in patients screened for alpha globin abnormalities. Significant findings include a rare double heterozygote mutation for Hb Q-Thailand and α+-thalassemia (-αQT/-α3.7) and the discovery of an uncharacterized 204bp deletion in HBA2.
- Subjects
ALPHA globulins; GENETIC mutation; HEMOGLOBINS; POLYMERASE chain reaction; NUCLEOTIDES; POLYMERIZATION
- Publication
UBC Medical Journal, 2011, Vol 2, Issue 2, p21
- ISSN
1920-7425
- Publication type
Abstract