P267 HLA haplotype structure in an european population

Aim This is a study of the haplotype frequency and distribution in an European population. In order to study the gene structure of HLA haplotypes, these haplotypes must be determined in a large sample from a given population. Diploid combinations of alleles from different loci must be placed in phase with each other. [Two other parallel studies are performed in two other ethnic populations.]. Methods Approximately 6000 samples come from an European collected for disease association. HLA typing is based on Mia Fora next-generation sequencing by Immucor. The following loci are included: A, B, C, DRB1, DRB345, DQA1, DQB1, DPA1 and DPB1. A modification of the EM algorithm was used to determine the haplotypes in the population. Linkage disequilibrium is performed by means of 2 × 2 contingency tables. Results Full 2 × 2 contingency tables, for each pair of variables, with their corresponding chi-square, p value and other measures of correlation are presented for the following pairs of HLA loci or groups of loci: 1) B vs. C, 2) DRB1 vs. DRB345, 3) DQA1 vs. DQB1, 4) DPA1 vs. DPB1, 5) A vs. B-C, 6) DRB1-DRB345 vs. DQA1-DQB1, 7) DPA1-DPB1 vs. DRB1-DRB345-DQA1-DQB1, and 8) A vs. DRB1-DRB345-DQA1-DQB1. Conclusions Results may be biased by the disease association in this project. (The disease in question cannot be disclosed at this time.) Nevertheless, the identity of the haplotype itself will not be affected by this bias. One of the main finding in this study is that, contrary to what is generally believed, NGS does not disclose a hidden abundance of HLA alleles, it rather helps us characterise in full detail alleles we were already familiar with. This study shows the association of HLA alleles with alleles in other loci. The second main finding in this study is that in those cases where more than one genetic variant is represented by a single previously known protein allele, the linkage disequilibrium measures increase significantly when this genetic variants are taken into account individually.