Scientific Publications by FDA Staff

Vox Sang 2006 Jul;91(1):81-7

Dombrock gene analysis in Brazilian people reveals novel alleles.

Baleotti W Jr, Rios M, Reid ME, Hashmi G, Fabron A Jr, Pellegrino J Jr, Castilho L

Castilho L, Univ Estadual Campinas, Hemoctr, Rua Carlos Chagas,480,Caixa Postal 6198,Barao Ger, BR-13081970 Campinas, SP, Brazil Univ Estadual Campinas, Hemoctr, BR-13081970 Campinas, SP, Brazil Hemoctr, Fac Med, Marilia, SP, Brazil US FDA, DETTD, OBRR, CBER, Rockville, MD 20857 USA New York Blood Ctr, New York, NY 10021 USA BioArray Solut, Warren, NJ USA

Background and Objectives The Do(a) and Do(b) polymorphisms are associated with three single nucleotide polymorphisms (SNPs) in exon 2 of the DO gene: 378C/T, 624T/C and 793A/G for the DOA and DOB alleles, respectively. The SNPs 350C/T (JO allele) and 323G/T (HY allele) are associated with the Jo(a-) and Hy-negative phenotypes. Recently, two new DO alleles [DOB-SH (378C, 624C, 793G) and DOA-HA (378T, 624T, 793A)] were identified using microarray technology. Although the molecular background of Dombrock alleles is well defined, no studies have been conducted in the Brazilian population. Materials and Methods We employed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based assays and a microarray assay to determine the frequency of the DO alleles (DOA, DOB, HY1, HY2 and JO) in Brazilians. We tested DNA of 288 Brazilians from three different ethnic groups by PCR-RFLP to determine the 793A/G (DOA/DOB), 323G/T (HY), 350C/T (JO) and 898C/G (HY1/HY2) SNPs. We also tested DNA from 162 blood donors by using the HEA Beadchiptrade mark assay to determine the 378C/T, 624T/C, 793A/G (DOA/DOB), 350C/T (JO allele) and 323G/T (HY) SNPs. Results Two novel allele combinations were found in our samples: the DOB allele (793G and 323G) associated with 898G (DOB-WL); and an allele carrying the nucleotides 378C, 624C, 793A and 323G (DOA-SH). We also found the DOB-SH and DOA-HA.alleles recently reported. Conclusions Our data demonstrate high heterogeneity of DO alleles in the Brazilian population. Our study also highlights the importance of testing a cohort of different populations to determine DO haplotypes and of establishing reliable genotyping tests for predicting Do(a)/Do(b) status.