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UNUSUAL DRB1-DQA1-DQB1 HAPLOTYPES SEEN IN CAUCASIANS, HISPANICS AND AFRICAN AMERICANS USING DRB1 HIGH RESOLUTION, DQA1/DQB1 CO-AMPLIFICATION AND HLA-A AND B PCR/SSO LINEAR ARRAYS.
T.L. Bugawan 1, J. Ching 1, S.L. Glaser 2, E.M. John 2, C.A. Clarke 2, T. Harasty 2, M. Agleham 3 and H.A. Erlich 1. 1 Human Genetics, Roche Molecular Systems, Alameda, CA ; 2 Northern CA Cancer Center, Fremont, CA and 3 Children's Hospital Research Institute, Oakland, CA .
A specific PCR amplification of the DRB1 locus was accomplished using eight 5
and one 3 primers. Hybridization of the biotinylated PCR products to a panel of 81 SSOP in a linear array format, which allows high resolution typing without separate amplification of DRB1 alleles, was used to genotype 155 Caucasians, 182 Hispanics and 140 African Americans. These samples were also typed for the DQA1, DQB1, A and B. The DQ typing was done using a co-amplification of DQA1/DQB1 with locus specific primers. Bw4 and Bw6 group specific primers were used for high resolution typing of HLA-B. Greater DR-DQ haplotype diversity was observed among African Americans and Hispanics than Caucasian population groups: 26 haplotypes (n>4) in Hispanics, 33 in African Americans and 18 in Caucasian were observed. This increased DR-DQ haplotype diversity may be attributable to admixture as well as to the greater genetic diversity generally observed among populations of African descent. Analysis of DRB1-DQB1 haplotypes revealed some rare/unusual haplotypes among African American and Hispanic populations. The DRB1*1303-DQA1*0201-DQB1*0201, is present in both Hispanics (f=0.003), and African American (f=0.021). DRB1*1302-DQA1*0301-DQB1*0201 haplotype is present in African American (f=0.004) while DRB1*1402-DQA1*0201-DQB1*0201 is seen only in Hispanics. Another unusual haplotype seen only in African Americans in this study is DRB1*1503-DQA1*0301-DQB1*0201. These unusual haplotypes were presumably generated by recombination between the DQA1 and the DRB1 loci.