Identification of 2127 new HLA class I alleles in potential stem cell donors from Germany, the United States and Poland

We describe 2127 new human leukocyte antigen (HLA) class I alleles found in registered stem cell donors. These alleles represent 28.9% of the currently known class I alleles. Comparing new allele sequences to homologous sequences, we found 68.1% nonsynonymous nucleotide substitutions, 28.9% silent mutations and 3.0% nonsense mutations. Many substitutions occurred at positions that have not been known to be polymorphic before. A large number of HLA alleles and nucleotide variations underline the extreme diversity of the HLA system. Strikingly, 156 new alleles were found not only multiple times, but also in carriers of various parentage, suggesting that some new alleles are not necessarily rare. Moreover, new alleles were found especially often in minority donors. This emphasizes the benefits of specifically recruiting such groups of individuals.

[1]  S. Y. Yang,et al.  Locus-specific amplification of HLA class I genes from genomic DNA: locus-specific sequences in the first and third introns of HLA-A, -B, and -C alleles. , 1995, Tissue antigens.

[3]  E. Adams,et al.  The Origins of HLA‐A,B,C Polymorphism , 1995, Immunological reviews.

[4]  M. Torres,et al.  Nomenclature for factors of the HLA system. , 2011, Bulletin of the World Health Organization.

[5]  S. E. Marsh.  Nomenclature for factors of the HLA system, update March 2013. , 2013, Tissue antigens.

[6]  James Robinson,et al.  The IMGT/HLA database , 2008, Nucleic Acids Res..

[7]  Harriet Noreen,et al.  Common and well-documented HLA alleles: report of the Ad-Hoc committee of the american society for histocompatiblity and immunogenetics. , 2007, Human immunology.

[8]  V. Lange,et al.  High-resolution HLA haplotype frequencies of stem cell donors in Germany with foreign parentage: how can they be used to improve unrelated donor searches? , 2013, Human immunology.

[9]  G. Ehninger,et al.  Criteria for initiation and evaluation of minority donor programs and application to the example of donors of Turkish descent in Germany , 2009, Bone Marrow Transplantation.

[10]  W. Bodmer,et al.  Nomenclature for factors of the HLA system, 2010 , 2010, Tissue antigens.

[11]  S. Y. Yang,et al.  Dimorphic primers derived from intron 1 for use in the molecular typing of HLA-B alleles. , 1997, Tissue antigens.

[12]  P. D. De Jager,et al.  Genetic risk variants in African Americans with multiple sclerosis , 2013, Neurology.

[13]  S. Marsh.  Nomenclature for factors of the HLA system, update February 2009. , 2009, Tissue antigens.

[14]  Steven G.E. Marsh,et al.  Nomenclature for factors of the HLA system, update , 2007 .