Determining the cause of patchwork HBA1 and HBA2 genes: recurrent gene conversion or crossing over fixation events.
OBJECTIVE
Recombinations are common between the two homologous alpha-globin genes. We report on the identification and characterization of two patchwork alpha-globin genes.


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consists primarily of the HBA1 gene sequence except for a small segment of IVSII in which an octanucleotide segment has been replaced by an HBA2 -specific nucleotide.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primarily of the HBA2 gene sequence except for a segment of IVSII in which HBA2 -specific nucleotides at two sites have been replaced by HBA1-specific sequences.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.


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
HY
Department of Pediatric Medicine, KK Women's & Children's Hospital, Singapore.
Luo
Hong-Yuan
HY
Wang
Wen
W
Ho
Julia F V
JF
Najmabadi
Hossein
H
Ng
Ivy S L
IS
Steinberg
Martin H
MH
Chui
David H K
DH
Chong
Samuel S
SS
D000293:Adolescent; D000483:Alleles; D001483:Base Sequence; D003434:Crossing Over, Genetic / Q000235:genetics*; D005260:Female; D005785:Gene Conversion / Q000235:genetics*; D006442:Glycated Hemoglobin / Q000235:genetics*; D006443:Hemoglobin A2 / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data
D006442:Glycated Hemoglobin; D006443:Hemoglobin A2