Differences in the central major histocompatibility complex between humans and chimpanzees. Implications for development of autoimmunity and acquired immune deficiency syndrome.
Chimpanzees (Pan Troglodytes) and humans are closely related and belong to the same subfamily, Homininae. The approximately 1.8% genetic difference that exists between humans and the chimpanzees must be responsible for observed differences between these two species. It has been shown that chimpanzees can be infected with HIV, but AIDS has not been reported. Furthermore, the prevalence of autoimmune diseases may be low in this species. For instance, type II diabetes occurs, but type I (autoimmune) diabetes (IDDM), to our knowledge, has not been reported. In humans, susceptibility genes for MG and IDDM have been localized to 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 shown by PFGE, the TNF to Patr-B region in the chimpanzees is approximately 130-160 kb shorter than the equivalent in humans. Southern and sequence analyses indicate that the deletions in chimpanzees (insertions in humans) include one copy of CL (approximately 10 kb) and the X sequences (< 30 kb). Obviously, other deletions/insertions (approximately 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 be relevant to the observed functional differences. We demonstrate here a strategy to identify critical genes responsible for disease development.
Leelayuwat
C
C
Department of Clinical Immunology, Royal Perth Hospital, Western Australia.
Zhang
W J
WJ
Abraham
L J
LJ
Townend
D C
DC
Gaudieri
S
S
Dawkins
R L
RL
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D002461:Cell Line, Transformed; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D003001:Cloning, Molecular; D015894:Genome, Human; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid