Project: Genetic Diversity and Function of non-classical HLA genes and HLA Pseudogenes

Genetic Diversity and Function of non-classical HLA genes and HLA Pseudogenes: Implications in Transplantation and MHC disease Association

Project leaders: David Sayer, Julie Di Cristofaro, Julien Paganini

Detailed project description:

The goal of this workshop component is to understand the genetic diversity, possible function, importance in transplantation, MHC disease association and MHC structure and evolution, of HLA and MIC pseudogenes
The MHC contains many HLA class 1 and class 1 like DNA sequences. These include the classical class 1 genes (HLA-A, -B and -C), the nonclassical class 1 genes (HLA-E, -F and -G) and the so-called Class 1 non-expressed or pseudogenes (HLA-H, -K, -J, -L and many others). Relative to the other Class 1 genes, the pseudogenes have been understudied, largely, (and as their name suggests) as a result of the assumption that these genes have no function. However, a recent study (Paganini et al, 2019) has identified that some HLA-H alleles have all the elements expected of a functional HLA class 1 gene. This begs the questions. Is HLA-H functional? What is its function?  Could other pseudogenes (HLA Class 1, HLA Class 2, MIC and others) be functional on some haplotypes? Could these pseudogenes be mismatched in transplantation? If so – what is the impact?
This workshop study is intended to address these questions.

Milestones in years:
2020-2021: Enrollment of participating laboratories, collection of typing data including conventionally typed HLA loci
2022: Analysis of data

Patient/sample description (if applicable, details, inclusion/exclusion criteria):
None excluded

Data required:
Any HLA gene, pseudogene or non classical HLA gene in addition to HLA-A,C,B,DRB1,DRB3,4,5,DQB1,DQA1,DPA1,DPB1.

Mimimum data requirements:
Full gene sequence (intron+exon and IMGT defined UTR) typing data in excel format with 4th field typing data for HLA-A, B,C,DRB1,DRB3,4,5, DQB1, DQA1,DPB1, DPA1.

Preferred data requirements:
Fastq files from full NGS runs of typing data that includes pseudogenes and non-classical HLA genes.
Exome sequence data.

Samples required:

Reagents / additional assays required:
Data from assays that include non classical HLA genes and HLA pseudogenes

Data infrastructure required:
Typing data in excel format