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#79
HLA-A-B-DRB1*-HAPLOTYPE FREQUENCIES OF THE GERMAN POPULATION.
Carlheinz R. Mueller M.D., Ph.D. 1, Ulrike Feldmann 1, Hans-Peter Eberhard M.Sc. 1, Daniel Baier Ph.D. 2 and Alexander Schmidt M.D., Ph.D. 2. 1 ZKRD, Zentrales Knochenmarkspender-Register, Ulm, Germany and 2 DKMS, Deutsche Knochenmarkspender-Datei, Tübingen, Germany .
The knowledge of HLA haplotype frequencies is an important basis for deciding on the donor search strategy for individual patients in need of a hematopoietic stem cell transplantation. Our frequency estimation is based on snapshot of the HLA phenotypes of 1,099,735 donors of the DKMS in March 2004. Donors of possibly Turkish origin were excluded by heuristically checking names. 412,494 of these individuals were typed for HLA-DRB1 at low or intermediate resolution and another 90,673 at high resolution level.
Estimation was performed using the well-known EM-algorithm. Only those 161 DRB1 alleles with positive frequency in a single locus analysis were considered; HLA-A and B were analyzed using serological nomenclature without associated antigens. All donors were used for low res. frequencies but for high res. frequencies donors only typed for A and B were excluded due to algorithmic limitations. Low resolution data were then used to correct a possible selection bias in the restricted data set.
The limitations of the data set (DRB1 missing or only low resolution) present a significant challenge to the optimization procedure. The sparse description matrix was 220 MB for low resolution and 1 GB for high resolution data in a compressed form. Terminating at a maximum frequency correction of 10e-8 the computation took 2 rsp. 9 days on a XEON 1.5 GHz. At high (low) resolution level for DRB1 we found positive frequency estimates only for about 10.000 (5.000) of the 100.000 (11.000) haplotypes considered. 1343 (1219) haplotypes are more frequent than 0.01% with a cumulative frequency of 86.0% (91.1%).