Dataset Information

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

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.

SUBMITTER: Norman PJ

PROVIDER: S-EPMC4540692 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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

Norman Paul J PJ Norberg Steve J SJ Nemat-Gorgani Neda N Royce Thomas T Hollenbach Jill A JA Shults Won Melissa M Guethlein Lisbeth A LA Gunderson Kevin L KL Ronaghi Mostafa M Parham Peter P

Immunogenetics 20150722 9

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 ai ...[more]

PMID: 26198775

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

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

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