Genetic Ancestry and HLA Matching in Bone Marrow Registries

The Major Histocompability Complex (MHC) is the most polymorphic genetic system in the human genome, and is also under very strong selection pressure, resulting in rapid genetic divergence between human populations for immune genes. The human leukocyte antigen (HLA) genes contained in the MHC region play a central role in the immune system as HLA proteins are used to distinguish self from non-self through antigen presentation to T-cells. Hematopoietic stem cell transplants (HSCT) can provide a curative therapy for patients with hematological diseases such as leukemia, but this requires a high degree of HLA matching between patient and donor for better outcome. While most human genetic variation exists within populations rather than between populations, the opposite is true for HLA.  Using a global database of over 14 million HLA-typed bone marrow donors, the National Marrow Donor Program (NMDP) is uniquely positioned to study genetic ancestry.   The development of classification or clustering techniques to assign subjects into populations based on HLA typing information aids in understanding why some patients don't find matches.  Mapping of HLA variation worldwide using geographical information systems (GIS) has the ability to transform donor recruitment and provide anthropological insights into the peopling of the earth. Genetic ancestry tools allow for more rapid identification of suitably matched donors, provide strategic direction for more targeted donor recruitment and optimize allocation of resources in order to serve more patients, specifically in underserved minority groups.