ArticleImmunogenetics2007
Full-length sequence analysis of the HLA-DRB1 locus suggests a recent origin of alleles.
Article in Immunogenetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- The origin of autoimmune diseases: is there a role for ancestral HLA-II haplotypes in immune hyperactivity.Frontiers in immunology · 2025Review
- Influence of Genetic Polymorphisms on Clinical Outcomes of Glatiramer Acetate in Multiple Sclerosis Patients.Journal of personalized medicine · 2021Review
- High-Throughput Sequencing to Investigate Associations Between HLA Genes and Metamizole-Induced Agranulocytosis.Frontiers in genetics · 2020Article
- HLA alleles and haplotypes observed in 263 US families.Human immunology · 2019Article
- Complete nucleotide sequence characterization of DRB5 alleles reveals a homogeneous allele group that is distinct from other DRB genes.Human immunology · 2019Article
- Article
- HLA Haplotype Validator for quality assessments of HLA typing.Human immunology · 2016Article
- Computer simulation of human leukocyte antigen genes supports two main routes of colonization by human populations in East Asia.BMC evolutionary biology · 2015Article
- NextGen sequencing reveals short double crossovers contribute disproportionately to genetic diversity in Toxoplasma gondii.BMC genomics · 2014Article
- The relevance of HLA sequencing in population genetics studies.Journal of immunology research · 2014Review
- A sequence-based approach demonstrates that balancing selection in classical human leukocyte antigen (HLA) loci is asymmetric.Human molecular genetics · 2013Article
- Sequencing and comparative analysis of the gorilla MHC genomic sequence.Database : the journal of biological databases and curation · 2013Article
- Fine scale analysis of crossover and non-crossover and detection of recombination sequence motifs in the honeybee (Apis mellifera).PloS one · 2012Article
- Extraordinary sequence divergence at Tsga8, an X-linked gene involved in mouse spermiogenesis.Molecular biology and evolution · 2011Article
- HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.PloS one · 2011Article
- Regulation of major histocompatibility complex class II gene expression, genetic variation and disease.Genes and immunity · 2010Review
- The chimpanzee Mhc-DRB region revisited: gene content, polymorphism, pseudogenes, and transcripts.Molecular immunology · 2009Article
- Evolution of duplicated beta-globin genes and the structural basis of hemoglobin isoform differentiation in Mus.Molecular biology and evolution · 2009Article
- Correlated evolution of nucleotide substitution rates and allelic variation in Mhc-DRB lineages of primates.BMC evolutionary biology · 2009Article
- Comparative genetics of a highly divergent DRB microsatellite in different macaque species.Immunogenetics · 2008Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The HLA region harbors some of the most polymorphic loci in the human genome. Among them is the class II locus HLA-DRB1, with more than 400 known alleles. The age of the polymorphism and the rate at which new alleles are generated at HLA loci has caused much controversy over the years. Previous studies have mostly been restricted to the 270 base pairs that constitute the second exon and represent the most variable part of the gene. Here, we investigate the evolutionary history of the HLA-DRB1 locus on the basis of an analysis of 15 genomic full-length alleles (10-15 kb). In addition, the variation in 49 complete coding sequences and 322 exon 2 sequences were analyzed. When excluding exon 2 from the analysis, the diversity at the synonymous sites was found to be similar to the intron diversity. The overall diversity in noncoding region was also similar to the genome average. The DRB1*03 lineage has been found in human, chimpanzee, bonobo, gorilla, and orangutan. An ancestral "proto HLA-DRB1*03 lineage" appeared to have diverged in the last 5 million years into the human-specific lineages *08, *11, *13, and *14. With exception to exon 2, both the coding- and the noncoding diversity suggests a recent origin (<1 million years ago) for most of the alleles at the HLA-DRB1 locus. Sites encoding for amino acids involved in antigen binding [antigen recognizing sites (ARS)] appear to have a more ancient origin. Taken together, the recent origin of most alleles, the high diversity between allelic lineages, and the ancient origin of sequence motifs in exon 2, is consistent with a relatively rapid generation of novel alleles by gene conversion like events.
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