TY - JOUR AU - HY Law, AU - HY Luo, AU - W Wang, AU - JF Ho, AU - H Najmabadi, AU - IS Ng, AU - MH Steinberg, AU - DH Chui, AU - SS Chong, PY - 2006/03/01 Y2 - 2024/03/28 TI - Determining the cause of patchwork HBA1 and HBA2 genes: recurrent gene conversion or crossing over fixation events JF - Haematologica JA - haematol VL - 91 IS - 3 SE - Comparative Studies DO - 10.3324/%x UR - https://haematologica.org/article/view/3878 SP - 297-302 AB - 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consists primarily of the HBA1 gene sequence except for a small segment of IVSII in which an octanucleotide segment has been replaced by an HBA2 -specific nucleotide.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primarily of the HBA2 gene sequence except for a segment of IVSII in which HBA2 -specific nucleotides at two sites have been replaced by HBA1-specific sequences.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. ER -