title: High resolution HLA haplotyping by imputation for a British population bioresource.
abstract: This study aimed to establish the occurrence and frequency of HLA alleles and haplotypes for a healthy British Caucasian population bioresource from Oxfordshire. We present the results of imputation from HLA SNP genotyping data using SNP2HLA for 5553 individuals from Oxford Biobank, defining one- and two-field alleles together with amino acid polymorphisms. We show that this achieves a high level of accuracy with validation using sequence-specific primer amplification PCR. We define six- and eight-locus HLA haplotypes for this population by Bayesian methods implemented using PHASE. We determine patterns of linkage disequilibrium and recombination for these individuals involving classical HLA loci and show how analysis within a haplotype block structure may be more tractable for imputed data. Our findings contribute to knowledge of HLA diversity in healthy populations and further validate future large-scale use of HLA imputation as an informative approach in population bioresources.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Old Road, Oxford OX3 7LJ, UK; Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
authors.forename: Matt J
authors.initials: MJ
authors.lastname: Neville
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Wanseon
authors.initials: W
authors.lastname: Lee
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Humburg
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wong
authors.affiliation: Transplant Immunology and Immunogenetics Laboratory, Oxford Transplant Centre, Churchill Hospital, Oxford OX3 7LJ, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Barnardo
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Old Road, Oxford OX3 7LJ, UK; Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Karpe
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. Electronic address: julian@well.ox.ac.uk.
authors.forename: Julian C
authors.initials: JC
authors.lastname: Knight
mesh_terms: D000328:Adult; D000483:Alleles; D001499:Bayes Theorem; D004739:England; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population / Q000379:methods; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D044465:White People / Q000235:genetics
chemical_list: D006680:HLA Antigens
keywords: Allele; Genotype; HLA; Imputation; Single nucleotide polymorphism