title: The nature of diversity and diversification at the ABO locus.
abstract: In this study we analyzed the complete genomic sequences, except intron 1, and 2 regulatory regions of 6 common (ABO*A101, ABO*A201, ABO*B101, ABO*O01, ABO*O02, and ABO*O03) and 18 rare ABO alleles, 3 of which were new. This was done by phylogenetic analysis and correlating sequence data with the ABO phenotypes. The study revealed multiple polymorphisms in noncoding regions. The intron-based phylogenetic analysis revealed 5 main lineages: ABO*A, ABO*B, ABO*O01, ABO*O02, and ABO*O03. The genomic sequences of most rare ABO alleles differed slightly from those of the common alleles. Singular mutations or hybrid alleles were most common, but a few exhibited mosaic sequence pattern containing multiple exon and/or intron motifs from other ABO lineages. Thus, both an accumulation of mutations as well as an assortment of the mutations by recombination seems to be responsible for the ABO gene diversity. The prevalence of replacement mutations indicates positive selection for allelic diversity. Phenotype-genotype correlation showed that sequence variations within the complete coding sequence can affect A- and B-antigen expression. All variant ABO*A/B alleles and one new ABO*O03-like allele were associated with weak ABO phenotypes. These findings are suggestive of the requirement of a comprehensive coding sequence database for sequence-based phenotype prediction.
authors.affiliation: Department of Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Str 1, D-30625 Hannover, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Seltsam
authors.forename: Michael
authors.initials: M
authors.lastname: Hallensleben
authors.forename: Anke
authors.initials: A
authors.lastname: Kollmann
authors.forename: Rainer
authors.initials: R
authors.lastname: Blasczyk
mesh_terms: D000017:ABO Blood-Group System; D000483:Alleles; D017931:DNA Primers / Q000737:chemistry; D019143:Evolution, Molecular; D005091:Exons; D005838:Genotype; D006801:Humans; D007438:Introns; D008957:Models, Genetic; D010641:Phenotype; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic
chemical_list: D000017:ABO Blood-Group System; D017931:DNA Primers