Determining the cause of patchwork HBA1 and HBA2 genes: recurrent gene conversion or crossing over fixation events. Academic Article uri icon

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  • BACKGROUND AND OBJECTIVES: Recombinations are common between the two homologous alpha-globin genes. We report on the identification and characterization of two patchwork alpha-globin genes. DESIGN AND METHODS: Multiplex polymerase chain reaction assays were performed to rule out the presence of alpha-globin gene deletions and triplications. The HBA1 (alpha1-globin) and HBA2 (alpha2-globin) genes were individually amplified and sequenced. RESULTS: Two variants of the HBA1 and HBA2 genes were identified. One variant allele, alpha121, consists primarily of the HBA1 gene sequence except for a small segment of IVSII in which an octanucleotide segment has been replaced by an HBA2 -specific nucleotide. Conversely, the alpha212 variant consists primarily of the HBA2 gene sequence except for a segment of IVSII in which HBA2 -specific nucleotides at two sites have been replaced by HBA1-specific sequences. Both variant alleles are found in individuals of different ethnicity, geographical origin, and haplotype backgrounds. The simplest model for the origins of these patchwork alleles is a single crossover between a normal allele and an existing recombinant allele such as the -alpha(3.7) single gene deletion or the alphaalphaalpha(anti3.7) triplicated allele, but we cannot exclude a reciprocal double crossover or a non-reciprocal gene conversion between misaligned HBA1 and HBA2 genes. INTERPRETATION AND CONCLUSIONS: The a-globin patchwork alleles have arisen independently on several occasions, most likely through a single crossover between a normal and a recombinant allele. Further studies are necessary to evaluate the possible effect of these changes on alpha-globin gene expression.


  • Law, Hai-Yang
  • Luo, Hong-Yuan
  • Wang, Wen
  • Ho, Julia FV
  • Najmabadi, Hossein
  • Ng, Ivy SL
  • Steinberg, Martin H
  • Chui, David Hing-kwei
  • Chong, Samuel S

publication date

  • March 2006