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#69
THE DISCOVERY OF NEW HLA ALLELES: WHAT KINDS OF VARIANTS ARE BEING DETECTED TODAY.
Ana M. Lazaro PhD 1, Kai Cao MD 1, Carly Masaberg 1, Noriko Steiner 1, Bin Tu 1, Jennifer Ng PhD 1, Robert Hartzman MD 2 and Carolyn K. Hurley PhD 1. 1 CW Bill Young Marrow Donor Program.Departments of Oncology and Pediatrics, Georgetown University, Washington, DC and 2 Naval Medical Research Center, Rockville, MD, USA .
Forty one new alleles of HLA-A,-B and -DRB1 have been described in our laboratory after typing 60,000 unrelated registry volunteers from the U.S. during the last two years, a frequency of 0.07%. The individuals were initially typed at intermediate resolution by an SSOP bead-based technology (One Lambda LabType). The new alleles were detected when one or more probes gave an unexpected reactivity pattern.
The alleles were found in individuals from all broad U.S. populations tested. No more than three new alleles were found within an allele group at any locus studied. Groups with 3 included A*0110, *0112, *0113; A*2432,*2441, *2450; B*270507, *2727, *2728. All of HLA-A, DRB1 and 73% HLA-B new alleles showed at least one amino acid change from known alleles. We observed 10% of alleles with nucleotide changes in addition to the site of variant probe hybridization. Substitutions altering previously non-polymorphic positions were found in 10% of new alleles. Further, 8 individuals (1.4%) carrying potential new alleles were found in a sample of 564 consecutively recruited African Americans evaluated by sequencing of commonly typed exons in which SSOP showed no variability. In summary, new alleles are still being observed in all populations routinely tested. Some are detected by unusual probe reactivity but more may be undetected unless sequencing is used. The frequency with which new alleles are encountered will vary in different populations.
Locus-No New Alleles White Af-Amer Latino Asian-Amer Native-Amer Unknown A-15 60% 13% 20% 7% B-22 64% 14% 9% 4.5% 4.5% 4.5% DRB1-4 60% 20% 20%