TY - JOUR
T1 - Genetic sophistication of human complement components C4A and C4B and RP-C4-CYP21-TNX (RCCX) modules in the major histocompatibility complex
AU - Chung, Erwin K.
AU - Van Yang, Yang
AU - Rennebohm, Robert M.
AU - Lokki, Marja Liisa
AU - Higgins, Gloria C.
AU - Jones, Karla N.
AU - Zhou, Bi
AU - Blanchong, Carol A.
AU - Yung, C. Yu
N1 - Funding Information:
We are indebted to the blood donors and patients who participated in this study. This work was supported by the National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant R01 AR43969 and National Institute of Diabetes and Digestive and Kidney Diseases grant P01 DK55546), a pilot grant from the Columbus Children’s Research Institute (297401), and Pittsburgh Supercomputing Center (through National Institutes of Health Center for Research Resources Cooperative Agreement grant 1P41 RR06009).
PY - 2002
Y1 - 2002
N2 - Human populations are endowed with a sophisticated genetic diversity of complement C4 and its flanking genes RP, CYP21, and TNX in the RCCX modules of the major histocompatibility complex class III region. We applied definitive techniques to elucidate (a) the complement C4 polymorphisms in gene sizes, gene numbers, and protein isotypes and (b) their gene orders. Several intriguing features are unraveled, including (1) a trimodular RCCX haplotype with three long C4 genes expressing C4A protein only, (2) two trimodular haplotypes with two long (L) and one short (S) C4 genes organized in LSL configurations, (3) a quadrimodular haplotype with four C4 genes organized in a SLSL configuration, and (4) another quadrimodular structure, with four long C4 genes (LLLL), that has the human leukocyte antigen haplotype that is identical to ancestral haplotype 7.2 in the Japanese population. Long-range PCR and PsJ.AI-RFLP analyses conclusively revealed that the short genes from the LSL and SLSL haplotypes are C4A. In four informative families, an astonishingly complex pattern of genetic diversity for RCCX haplotypes with one, two, three and four C4 genes is demonstrated; each C4 gene may be long or short, encoding a C4A or C4B protein. Such diversity may be related to different intrinsic strengths among humans to defend against infections and susceptibilities to autoimmune diseases.
AB - Human populations are endowed with a sophisticated genetic diversity of complement C4 and its flanking genes RP, CYP21, and TNX in the RCCX modules of the major histocompatibility complex class III region. We applied definitive techniques to elucidate (a) the complement C4 polymorphisms in gene sizes, gene numbers, and protein isotypes and (b) their gene orders. Several intriguing features are unraveled, including (1) a trimodular RCCX haplotype with three long C4 genes expressing C4A protein only, (2) two trimodular haplotypes with two long (L) and one short (S) C4 genes organized in LSL configurations, (3) a quadrimodular haplotype with four C4 genes organized in a SLSL configuration, and (4) another quadrimodular structure, with four long C4 genes (LLLL), that has the human leukocyte antigen haplotype that is identical to ancestral haplotype 7.2 in the Japanese population. Long-range PCR and PsJ.AI-RFLP analyses conclusively revealed that the short genes from the LSL and SLSL haplotypes are C4A. In four informative families, an astonishingly complex pattern of genetic diversity for RCCX haplotypes with one, two, three and four C4 genes is demonstrated; each C4 gene may be long or short, encoding a C4A or C4B protein. Such diversity may be related to different intrinsic strengths among humans to defend against infections and susceptibilities to autoimmune diseases.
UR - https://www.scopus.com/pages/publications/0036780616
U2 - 10.1086/342777
DO - 10.1086/342777
M3 - Article
C2 - 12226794
AN - SCOPUS:0036780616
SN - 0002-9297
VL - 71
SP - 823
EP - 837
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 4
ER -