Project: Creating Fully Representative MHC Reference Haplotypes

Project name: Creating Fully Representative MHC Reference Haplotypes

Project leader(s): Paul Norman

Detailed project description:

The human genome reference is a valuable resource for multiple branches of science, yet does not adequately represent human diversity, a shortcoming that is especially evident in the highly polymorphic MHC region. A fundamental endeavour of the IHIW was assembling a collection of DNA and cells from individuals identified as homozygous through large tracts of the MHC region. This collection proved invaluable for assay development in the H&I field and furthered our understanding of the MHC region; recently, we sequenced the entire collection of cell lines to full resolution. However, the IHIW cell lines represent mainly European individuals and an estimated 20-50% of European haplotypes. Thus, the majority of MHC haplotypes, both common and rare throughout the world, and including many associated with disease, are not yet covered. In this workshop component, we have begun collecting the next generation of IHIW MHC-homozygous samples in order to expand, diversify and modernize this critical community resource that has been foundational to the field. For this effort, we are seeking samples for individuals who have been identified by typing labs as homozygous through all of their HLA class I and/or HLA class II genes. We are also seeking those individuals from whole-genome SNP or sequencing studies having extensive homozygosity tracts covering at least 2Mbp of the MHC region. The main subjects of interest are non-European individuals or European individuals having less-common HLA haplotypes. We will perform targeted sequencing of the MHC region from DNA samples, and wherever possible create immortalized cell lines for use by the community. This project will be performed in collaboration with the NIH-sponsored HLA Region Genetics Consortium. The data will serve as a resource for investigators seeking to characterize variation across the MHC region for disease and population studies.


Milestones in years:

2020: Identify MHC region homozygous individuals

2021: Collect and Sequence 200 MHC-homozygous DNA samples

2022: Create fully-annotated MHC-region reference


Patient/sample description:

Samples identified as homozygous for HLA haplotypes that are not common in Europeans. No exclusion, but non-European individuals likely preferred.


Data required:

HLA genotype, or SNP data from the MHC-region, or whole-genome/whole exome sequence


Samples required:

We aim to collect 200 DNA samples, and expect many labs to each donate a small number of samples.


Reagents/additional assays required

Lymphocytes if available.