The Abantu phenotype in the ABO blood group system is due to a splice-site mutation in a hybrid between a new O1-like allelic lineage and the A2 allele
| Autor: | Martin L. Olsson, M. A. Chester, Bahram Hosseini-Maaf, E. Smart |
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| Rok vydání: | 2005 |
| Předmět: |
Population
Black People Locus (genetics) Cis AB Biology ABO Blood-Group System Exon Gene Frequency ABO blood group system Ethnicity Humans Genetic Testing RNA Messenger Allele Frameshift Mutation education Alleles Recombination Genetic Genetics education.field_of_study Splice site mutation Intron Exons Hematology General Medicine Molecular biology Introns Phenotype Mutation RNA Splice Sites |
| Zdroj: | Vox Sanguinis. 88:256-264 |
| ISSN: | 1423-0410 0042-9007 |
| DOI: | 10.1111/j.1423-0410.2005.00626.x |
| Popis: | Background and Objectives Many phenotypic variations in the expression of blood group A have been explained by variations in gene structure, but unresolved samples are frequently encountered in the reference laboratory. Among ABO subgroups, A b a n t u has the highest frequency in a specified population. The molecular basis of this phenotype is now described. Materials and Methods Blood from Black donors phenotyped as A b a n t u was subjected to genomic ABO screening and direct sequencing of polymerase chain reaction (PCR)-amplified ABO exons 1-7 and introns 2-6. Total RNA was extracted and ABO cDNA was synthesized by reverse transcription (RT)-PCR. Control material comprised Black South African, Swedish, Jordanian and Brazilian blood samples with common phenotypes. Results Genomic ABO typing indicated the presence of an A 2 allele in each A b a n t u donor, in combination with an 0 allele. No previously reported mutations associated with weak A or B expression were found. Direct sequencing indicated the common A 2 sequence with a single nucleotide deletion (AGGT>AGT) at the exon 4/intron 4 junction, predicted either to disrupt the reading frame (resulting in a premature stop codon) or to cause erroneous splicing (resulting in the exclusion of exon 4 from the mRNA). 0 mRNA, but no transcripts from the A b a n t u allele, could be detected. Surprisingly, the splice-site mutation was also found in 5% of 0 alleles in Black South Africans, but not in other blood donors, or in non-O 1 alleles. Utilizing intron polymorphisms, the A b a n t u allele was shown to be a recombination between a new allelic lineage (O 1 b a n t u ) and A 2 , with a cross-over region near exon 5. Conclusion The A b a n t u phenotype is caused by an O 1 b a n t u -A 2 hybrid at the ABO locus. |
| Databáze: | OpenAIRE |
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