title: Uncommon HLA alleles identified by hemizygous ultra-high Sanger sequencing: haplotype associations and reconsideration of their assignment in the Common and Well-Documented catalogue.
abstract: Although the number of HLA alleles still increases, many of them have been reported being uncommon. This is partly due to lack of full length gene sequencing, especially for those alleles belonging to an allele ambiguity in which the first discovered allele has been assigned as the most frequent one. As members of the working group on Common and Well Documented (CWD) alleles and since we implemented full length group-specific sequencing as standard method routinely, we have investigated the presence of presumably rare alleles in our collection of HLA typing data. We identified 50 alleles, that were not previously encountered as Common or Well Documented. Sixteen of them should be added to the CWD catalogue, since we encountered them in 5 or more unrelated individuals. Another 11 could be added, based upon our results and the data present in the IMGT database and the rare allele section of the allele frequencies database. Furthermore, tight associations were observed between several different alleles even at the level of synonymous and non-coding sequences. In addition, in several cases the uncommon allele was found to be more frequent than its common counterpart.
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands. Electronic address: c.voorter@mumc.nl.
authors.forename: Christina E M
authors.initials: CE
authors.lastname: Voorter
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Mathijs
authors.initials: M
authors.lastname: Groeneweg
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Lisette
authors.initials: L
authors.lastname: Groeneveld
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Marcel G J
authors.initials: MG
authors.lastname: Tilanus
mesh_terms: D000483:Alleles; D005787:Gene Frequency; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D057898:Hemizygote; D006650:Histocompatibility Testing; D006801:Humans; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D006680:HLA Antigens
keywords: Common and Well-Documented allele; Full length sequencing; Hemizygous sequencing; Human Leukocyte Antigen; Rare allele