The Alper lab studies the genetics of complex (polygenic) disease in humans, with a focus on autoimmunity, particularly within the genes of the major histocompatibility complex (MHC) of chromosome 6. Many human diseases of unknown origin, but mostly involving immune reactions against the patients’ own tissues, show associations with the MHC. Autoimmune diseases affect over 5% of the U.S. population, represent a major medical and public health challenge and many are rising in incidence at an alarming rate.
Specifically, Alper and colleagues investigate the relationship between genetic differences in the human MHC with differences in the immune function of a variety of "white blood cells," or leukocytes. Gene products of the human MHC are also sometimes called human leukocyte antigens (HLA), and are major proteins expressed on and within leukocytes. Many of these proteins are used by the body to differentiate "self" from foreign cells, and HLA proteins play a critical role in organ and tissue recognition and rejection after transplantation as well as in detecting foreign pathogens.
Over 100 expressed genes are located within the human MHC. As would be expected for a region that contains genes encoding proteins that help define "self," this region is among the most diverse of the human genome. The Alper lab often studies the blood of donors bearing conserved extended MHC haplotypes (CEHs) to explore control by these genes. Alper and colleagues established the concept of CEHs as a means of understanding the high degree of structural genetic fixity within relatively large stretches (e.g., the MHC) of the human genome. Although the lab has studied the MHC genetics of a number of immune functions and diseases, they are currently focused on four specific areas. These are the genetic mechanisms of autoimmunity—with a particular focus on type 1 diabetes (T1D), immunoglobulin deficiency (particularly IgA deficiency), the role of population admixture in the rising incidence of polygenic disease, and complement.