Very long haplotype tracts characterized at high resolution from HLA homozygous cell lines

Immunogenetics. 2015 Sep;67(9):479-85. doi: 10.1007/s00251-015-0857-y. Epub 2015 Jul 22.

Abstract

The HLA region of chromosome 6 contains the most polymorphic genes in humans. Spanning ~5 Mbp the densely packed region encompasses approximately 175 expressed genes including the highly polymorphic HLA class I and II loci. Most of the other genes and functional elements are also polymorphic, and many of them are directly implicated in immune function or immune-related disease. For these reasons, this complex genomic region is subject to intense scrutiny by researchers with the common goal of aiding further understanding and diagnoses of multiple immune-related diseases and syndromes. To aid assay development and characterization of the classical loci, a panel of cell lines partially or fully homozygous for HLA class I and II was assembled over time by the International Histocompatibility Working Group (IHWG). Containing a minimum of 88 unique HLA haplotypes, we show that this panel represents a significant proportion of European HLA allelic and haplotype diversity (60-95 %). Using a high-density whole genome array that includes 13,331 HLA region SNPs, we analyzed 99 IHWG cells to map the coordinates of the homozygous tracts at a fine scale. The mean homozygous tract length within chromosome 6 from these individuals is 21 Mbp. Within HLA, the mean haplotype length is 4.3 Mbp, and 65 % of the cell lines were shown to be homozygous throughout the entire region. In addition, four cell lines are homozygous throughout the complex KIR region of chromosome 19 (~250 kbp). The data we describe will provide a valuable resource for characterizing haplotypes, designing and refining imputation algorithms and developing assay controls.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Asian People / genetics
  • B-Lymphocytes / cytology
  • Cell Line
  • Chromosomes, Human, Pair 6 / genetics
  • Genes, MHC Class I / genetics*
  • Genes, MHC Class II / genetics*
  • Genome, Human / genetics*
  • Haplotypes / genetics
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class II / genetics*
  • Humans
  • Polymorphism, Single Nucleotide / genetics
  • White People / genetics

Substances

  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II