Reanalysis of sequence-based HLA-A, -B and -Cw typings: how ambiguous is today's SBT typing tomorrow.
The permanently increasing number of human leukocyte antigen (HLA)-alleles and the growing list of ambiguities require continuous updating of high-resolution HLA typing results. Two different kinds of ambiguities exist: the first, when two or more allele combinations have identical heterozygous sequences, and the second, when differences are located outside the analyzed region. The number of HLA-A, B and C alleles recognized in 1999 was almost tripled in 2006. Two hundred individuals, sequence-based typing (SBT) typed in the period from 1999 to 2002, were reanalyzed using the 2006 database. A final allele typing result of at least four digits was obtained for HLA-A, -B and -C by heterozygous sequencing of exons 2 and 3 and, if necessary, additional exons and/or allele-specific sequencing. Storage of the individual sequences in a specially developed database enabled reanalysis with all present and future HLA releases. In the 5-year period HLA-A, -B and -C typing results became ambiguous in 37%, 46% and 41% of the cases. Most were because of differences outside the analyzed region; ambiguities because of different allele combinations with identical heterozygous sequences were present in 7%, 8% and 13% of the HLA-A, -B and -C typings. These results indicate that within 5 years, approximately half of the HLA SBT typings become ambiguous.
Voorter
C E M
CE
Tissue Typing Laboratory, University Hospital Maastricht, Maastricht, The Netherlands.
Mulkers
E
E
Liebelt
P
P
Sleyster
E
E
van den Berg-Loonen
E M
EM
D000483:Alleles; D030541:Databases, Genetic / Q000639:trends; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics*; D006579:Heterozygote; D006650:Histocompatibility Testing / Q000639:trends; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA / Q000639:trends
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens