title: 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.
authors.affiliation: Departments of Structural Biology and Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA, paul.norman@stanford.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Norman
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Norberg
authors.forename: Neda
authors.initials: N
authors.lastname: Nemat-Gorgani
authors.forename: Thomas
authors.initials: T
authors.lastname: Royce
authors.forename: Jill A
authors.initials: JA
authors.lastname: Hollenbach
authors.forename: Melissa
authors.initials: M
authors.lastname: Shults Won
authors.forename: Lisbeth A
authors.initials: LA
authors.lastname: Guethlein
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Gunderson
authors.forename: Mostafa
authors.initials: M
authors.lastname: Ronaghi
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology; D002460:Cell Line; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005805:Genes, MHC Class I / Q000235:genetics*; D005802:Genes, MHC Class II / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II