The overall objective of the planned research is the further definition of genetic control of proteins in the human complement system. In particular, subtypes of common C4A and C4B alleles will be sought in order to provide more informative complotypes for the identification of extended major histocompatibility complex haplotypes as markers for disease susceptibility, for immune response and immune suppression genes and for previously isolated human populations. The subtypes of common C4A and C4B alleles will be identified by isoelectric focusing of desialated whole molecules and by apparent size polymorphisms in C4 Beta and Gamma chains detected by sodium dodecyl sulfate electrophoresis. Any such variation detected will be studied in families to provide allele frequencies, evidence for inheritance and relationship to other major histocompatibility complex markers, including restriction fragment length polymorphisms in genomic DNA. Other studies will define genetic polymorphism in human Clq and Cls. For Clq, charge variation in A, B and C subunits will be investigated and localized to collagen-like stalk and stem or to globular head fragments. For Cls, the variation will be localized to one chain or the other of Cls, inheritance will be shown in family studies and population allele frequencies will be determined. Linkage relationships will be studied among possible loci for the subunits of Cq, between these and that for Cls, and between the Cl loci and other complement loci. From these studies, we hope to obtain new insights into genetic control of C4, Clq and Cls and into the evolution of the complement system in man.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI014157-15
Application #
3125655
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1977-12-01
Project End
1990-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
15
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Immune Disease Institute, Inc.
Department
Type
DUNS #
115524410
City
Boston
State
MA
Country
United States
Zip Code
02115
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Crawford, K; Alper, C A (2000) Genetics of the complement system. Rev Immunogenet 2:323-38
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Clavijo, O P; Delgado, J C; Awdeh, Z L et al. (1998) HLA-Cw alleles associated with HLA extended haplotypes and C2 deficiency. Tissue Antigens 52:282-5
Alper, C A (1998) A history of complement genetics. Exp Clin Immunogenet 15:203-12
Simon, S; Truedsson, L; Marcus-Bagley, D et al. (1997) Relationship between protein complotypes and DNA variant haplotypes: complotype-RFLP constellations (CRC). Hum Immunol 57:27-36
Garcia-Merino, A; Alper, C A; Usuku, K et al. (1996) Tumor necrosis factor (TNF) microsatellite haplotypes in relation to extended haplotypes, susceptibility to diseases associated with the major histocompatibility complex and TNF secretion. Hum Immunol 50:11-21

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