P245 Immune response genetics and the 1000 genomes samples: toward application in precision medicine

Abstract

Aim The practice of using genetic information as guidance for clinical application, so called precision medicine, has been in use for over 30 years in donor and recipient matching for HLA in hematopoietic cell transplantation. As precision medicine moves into the mainstream of clinical practice, a driving force is the availability of novel technologies and the creation of population datasets that can inform the details of genetic variation at immune response loci. Among the most polymorphic loci in the human genome are HLA class I and class II, MICA/B and KIR gene families. These genes are central to the immune response, which in turn is central to most common diseases. We are using resources from the 1000 Genome Project to rigorously evaluate a novel next generation genotyping protocol, to refine existing 1000 genome data resources for population and data mining studies, and to supplement currently available HLA and immune response genetic data sets. Methods The 1000 Genomes Project, one of the largest public catalogues of human variation and genotype data, provides panels for additional studies, comprising 2,542 DNA samples from 26 ethnic populations available through the International Genome Sample Resource. We are using a novel and extensible next generation sequencing protocol for genotyping of HLA, MICA/B and KIR. Results To date, 800 samples have been fully genotyped for HLA, MICA/B and KIR. The data are examined to identify allele groups and haplotypes that define each of the 26 populations. HLA class I intron sequence variation between populations is examined for potential relevance in the transplant setting and in disease association studies in general. Once published all data will be deposited in publically accessible databases. Conclusions This study demonstrates that novel genotyping methods can be used to acquire the detail of the genetics of the immune response sufficient for application in precision medicine.