title: HLA Haplotype Validator for quality assessments of HLA typing.
abstract: HLA alleles are observed in specific haplotypes, due to Linkage Disequilibrium (LD) between particular alleles. Haplotype frequencies for alleles in strong LD have been established for specific ethnic groups and racial categories. Application of high-resolution HLA typing using Next Generation Sequencing (NGS) is becoming a common practice in research and clinical laboratory settings. HLA typing errors using NGS occasionally occur due to allelic sequence imbalance or misalignment. Manual inspection of HLA genotypes is labor intensive and requires an in-depth knowledge of HLA alleles and haplotypes. We developed the "HLA Haplotype Validator (HLAHapV)" software, which inspects an HLA genotype for both the presence of common and well-documented alleles and observed haplotypes. The software also reports warnings when rare alleles, or alleles that do not belong to recognized haplotypes, are found. The software validates observable haplotypes in genotype data, providing increased confidence regarding the accuracy of the HLA typing, and thus reducing the effort involved in correcting potential HLA typing errors. The HLAHapV software is a powerful tool for quality control of HLA genotypes prior to the application of downstream analyses. We demonstrate the use of the HLAHapV software for identifying unusual haplotypes, which can lead to finding potential HLA typing errors.
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA; Children's Hospital Oakland Research Institute, Oakland, CA, USA. Electronic address: kazutoyo@stanford.edu.
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Osoegawa
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Mack
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Udell
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Noonan
authors.affiliation: National Marrow Donor Program, Minneapolis, MN, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Ozanne
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Trachtenberg
authors.affiliation: National Marrow Donor Program, Minneapolis, MN, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Prestegaard
mesh_terms: D000483:Alleles; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D005787:Gene Frequency; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006650:Histocompatibility Testing; D006801:Humans; D015810:Linkage Disequilibrium; D015203:Reproducibility of Results; D012984:Software; D064878:Web Browser
chemical_list: D006680:HLA Antigens
keywords: HLA-B∼C haplotype block; HLA-DRB3/4/5∼DRB1∼DQB1 haplotype block; Haplotype; Linkage Disequilibrium