An evaluation of quality and accuracy of imputed HLA Class I and II genotype assignment data generated from High Density single nucleotide polymorphism gene chips and assessing the suitability of this method as a cost effective approach for determining ‘extended HLA region’ typing of stored retrospective transplant DNA samples

Principal Investigator – Kay Poulton

Matching kidney recipient-donor HLA tissue types is recognised as a critical factor for renal transplant outcome. Methods to define the large number of tissue types within populations and establish an individual’s tissue type have changed greatly over the last 50 years; most methods used now are based on DNA based molecular techniques to define types at the gene level. This is time consuming and expensive. The HLA region is also rich in other variable genes, of which many encode important immune functions but are not routinely defined as part of the clinical service. It is unclear how much these genes influence transplant outcome but some effect is likely as transplants between identical twins and HLA identical sibling-pairs do better than well matched but unrelated donor-recipient transplants. Research approaches to identify genetic factors in common diseases use high-throughput, low-cost methods where over one million gene variants can be tested on an individual using a single test microchip. Although these were not originally designed for HLA typing, ‘open source’ computer programmes can be used to define high-resolution HLA types. In addition, variation in other immune genes can also be defined. This offers important possibilities to
(1) type a wider range of HLA region genes cheaply in a cost effect way, and
(2) provide a mechanism for identifying other genetic factors involved in rejection, antibody production and disease recurrence post-transplant.
This proposed study will establish our ability to perform large scale data analyses and to will examine the quality of available large imputed HLA data sets. If this approach is valid, funding will be sought for further research using our extensive laboratory biobank of DNA samples from donor-recipient pairs.