DIFFERENCES IN THE CENTRAL MAJOR HISTOCOMPATIBILITY COMPLEX BETWEEN HUMANS AND CHIMPANZEES - IMPLICATIONS FOR DEVELOPMENT OF AUTOIMMUNITY AND ACQUIRED-IMMUNE-DEFICIENCY-SYNDROME

Chimpanzees (Pan Traglodytes) and humans are closely related and belon g to the same subfamily, Homininae. The approximately 1.8% genetic dif ference that exists between humans and the chimpanzees must be respons ible for observed differences between these two species. It has been s hown that chimpanzees can be infected with HIV, but AIDS has not been reported. Furthermore, the prevalence of autoimmune diseases may be lo w in this species. For instance, type Il diabetes occurs, but type I ( autoimmune) diabetes (IDDM), to our knowl edge, has not been reported. In humans, susceptibility genes for MG and IDDM have been localized t o the region between TNF and HLA-B. This region may also influence the rate of progression to death after HIV infection. We have identified differences in this region between humans and the chimpanzees. As show n by PFGE, the TNF to Patr-B region in the chimpanzees is approximatel y 130-160 kb shorter than the equivalent in humans. Southern and seque nce analyses indicate that the deletions in chimpanzees (insertions in humans) include one copy of CL (similar to 10 kb) and the X sequences (< 30 kb). Obviously, other deletions/insertions (similar to 120 kb) need to be identified. Since CL has been shown to be transcribed, the results imply the lack of the gene or, at least, a different gene copy number in the chimpanzees, and we propose that such differences may b e relevant to the observed functional differences. We demonstrate here a strategy to identify critical genes responsible for disease develop ment.