Sequencing Protocols for Detection of HLA Class I Polymorphism

The human leukocyte antigen (HLA) genes located within the human major histocompatibility complex on chromosome 6 are probably the most polymorphic functional genetic loci studied to date. The functional HLA genes encode protein molecules that function in antigen presentation within the immune response. Polymorphism within these genes influences diversity of the immune response against different pathogenic infections. Such polymorphism within the human population is considered an advantage, as diversity in immune responses allows some individuals to be better than others at combating certain infections and thus ensuring survival of the species. However, this polymorphism also serves as a major barrier against the transplantation of human organs and stem cells, where HLA incompatibility between donor and recipient can lead to graft rejection or, in the case of stem cells, graft vs host disease. The study of HLA polymorphism has been led by transplantation biologists because of the implication of HLA matching in improving transplant outcome. HLA polymorphism data is also utilized in anthropological studies, where the frequency of HLA alleles can be used as a marker for analysis of population genetics. As HLA proteins function in the immune response, it is not surprising to find association between different HLA types and immunerelated diseases, such as autoimmune disease, and in this field HLA typing serves as a disease marker in genetic studies.