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Molecular, serological and genetic studies on two new HLA-DRB1 alleles--HLA-DRB1*0704 and HLA-DRB1*1507

C Darke1, M G Guttridge, J Street

  • 1Regional Tissue Typing Laboratory, Welsh Blood Service, Cardiff, United Kingdom. cdarke@wbmdr.demon.co.uk

Tissue Antigens
|January 6, 2001
PubMed

Insights

Two novel Human Leukocyte Antigen - DRB1 (HLA-DRB1) alleles, DRB1*0704 and DRB1*1507, were identified through routine typing. These rare alleles were characterized by specific nucleotide and amino acid differences from known alleles.

Area of Science:

  • Immunogenetics
  • Molecular Biology
  • Human Leukocyte Antigen (HLA) System

Background:

  • Routine Human Leukocyte Antigen - DRB1 (HLA-DRB1) typing of bone marrow donors can reveal novel alleles.
  • Unexpected associations with other HLA loci (DRB4, DRB5, DQB1) can indicate the presence of new alleles.

Purpose of the Study:

  • To identify and characterize new Human Leukocyte Antigen - DRB1 (HLA-DRB1) alleles.
  • To determine the genetic and population frequency of these novel alleles.

Main Methods:

  • Polymerase chain reaction (PCR)-based typing for Human Leukocyte Antigen - DRB1 (HLA-DRB1) allele identification.
  • Nucleotide sequencing to define allelic differences.
  • Serological and family/population studies for specificity assignment and haplotype analysis.

Main Results:

  • Two new Human Leukocyte Antigen - DRB1 (HLA-DRB1) alleles, DRB1*0704 and DRB1*1507, were discovered.
  • DRB1*0704 differs from DRB1*0701 by five nucleotides, resulting in two amino acid substitutions.
  • DRB1*1507 differs from DRB1*1501 by one nucleotide, causing one amino acid substitution.

Conclusions:

  • The new alleles, HLA-DRB1*0704 and HLA-DRB1*1507, were unequivocally assigned specificities HLA-DR7 and HLA-DR15, respectively.
  • Family and population studies provided insights into their associated haplotypes.
  • The low frequency (<0.01% phenotype, <0.00003 gene) in a large donor registry suggests these are rare alleles.

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