Construction of full-length Japanese reference panel of class I HLA genes with single-molecule, real-time sequencing

Pharmacogenomics J. 2019 Apr;19(2):136-146. doi: 10.1038/s41397-017-0010-4. Epub 2018 Jan 19.

Abstract

Human leukocyte antigen (HLA) is a gene complex known for its exceptional diversity across populations, importance in organ and blood stem cell transplantation, and associations of specific alleles with various diseases. We constructed a Japanese reference panel of class I HLA genes (ToMMo HLA panel), comprising a distinct set of HLA-A, HLA-B, HLA-C, and HLA-H alleles, by single-molecule, real-time (SMRT) sequencing of 208 individuals included in the 1070 whole-genome Japanese reference panel (1KJPN). For high-quality allele reconstruction, we developed a novel pipeline, Primer-Separation Assembly and Refinement Pipeline (PSARP), in which the SMRT sequencing and additional short-read data were used. The panel consisted of 139 alleles, which were all extended from known IPD-IMGT/HLA sequences, contained 40 with novel variants, and captured more than 96.5% of allelic diversity in 1KJPN. These newly available sequences would be important resources for research and clinical applications including high-resolution HLA typing, genetic association studies, and analyzes of cis-regulatory elements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Genetic Variation*
  • Genome, Human / genetics*
  • Genotype
  • High-Throughput Nucleotide Sequencing*
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Testing
  • Humans
  • Japan
  • Sequence Analysis, DNA

Substances

  • Histocompatibility Antigens Class I