High-resolution genotyping of HLA-DQA1 in the GoKinD study and identification of novel alleles HLA-DQA1*040102, HLA-DQA1*0402 and HLA-DQA1*0404

Tissue Antigens. 2005 May;65(5):448-58. doi: 10.1111/j.1399-0039.2005.00389.x.

Abstract

In order to achieve high-resolution HLA-DQA1 genotyping, it is necessary to identify polymorphisms in exons 1, 2 and 3. We present a high-resolution sequence-based typing (SBT) strategy for genotyping exons 1, 2 and 3 of the polymorphic HLA-DQA1 locus. This method is an improvement upon previously presented methods, because it utilizes the minimum number of SSP-PCR assays to obtain clear DNA sequence in both the forward and reverse directions of all three exons. All known HLA-DQA1 alleles are resolved with the exception of HLA-DQA1*010101 and HLA-DQA1*010102 for which the distinguishing polymorphism is located in exon 4 and does not result in an amino acid change. This method has enabled our laboratory to identify three new HLA-DQA1 alleles - HLA-DQA1*040102, HLA- DQA1*0402 and HLA-DQA1*0404 - in the Genetics of Kidneys in Diabetes (GoKinD) study population. Additionally, we present single-allele amplification methods, which identify the coding sequences of HLA-DQA1 exons 1, 2, 3, intron 2 and 300 bp of the HLA-DQA1 promoter (QAP). This study, also describes the QAP for most of the known HLA-DQA1 alleles, three HLA-DQA2 promoter sequences and the intron 2 sequences for HLA-DQA1*040101, HLA-DQA1*040102, HLA-DQA1*0402 and HLA-DQA1*0404.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Base Sequence
  • Canada / epidemiology
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetic Nephropathies / epidemiology
  • Diabetic Nephropathies / genetics*
  • Exons / genetics
  • Genes, MHC Class II*
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-DQ Antigens / genetics*
  • HLA-DQ alpha-Chains
  • Haplotypes / genetics
  • Histocompatibility Testing / methods*
  • Humans
  • Molecular Sequence Data
  • Polymerase Chain Reaction / methods
  • Promoter Regions, Genetic / genetics
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology, Nucleic Acid
  • United States / epidemiology

Substances

  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQA1 antigen