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PMID: 3018042 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Polymorphism of the human complement C4 and steroid 21-hydroxylase genes. Restriction fragment length polymorphisms revealing structural deletions, homoduplications, and size variants.

The Journal of clinical investigation ·Vol. 78 ·No. 3 ·1986-09-00 ·Pages 650-7

Schneider PM, Carroll MC, Alper CA, Rittner C, Whitehead AS, Yunis EJ, Colten HR

Abstract

Several autoimmune disorders as well as congenital adrenal hyperplasia (CAH) are either associated or closely linked with genetic variants of the fourth component of complement (C4A and C4B) and the enzyme steroid 21-hydroxylase (21-OH). These proteins are encoded by genes that are located downstream from the genes for complement proteins, C2 and factor B (BF) between HLA-B and -DR in the major histocompatibility complex (MHC). Previous studies of variants and null alleles were based on electrophoretic mobility of C4 protein and linkage with disease phenotypes. These data did not permit analysis of the basis for the observed null alleles and duplicated variants. We studied this region of the MHC in 126 haplotypes for a structural analysis of the four adjacent loci, C4A, 21-OHA, C4B, and 21-OHB. About half of the C4 genes typed as C4 null are deleted and several unrecognized homoduplicated C4 alleles were detected. Hence the frequencies of different C4 structural variants must be recalculated based on a direct analysis of the genes. Analysis of the C4/21-OH genes of patients with the classical (salt-wasting) form of CAH showed that some involve a deletion of the C4B and 21-OHB genes; whereas for two only the 21-OHB gene is deleted, i.e., the C4B gene is present. Together, these data provide a better understanding of the mechanisms generating and importance of deleted C4 and 21-OH null alleles in human disease.

MeSH Terms
Adrenal Hyperplasia, Congenital/genetics Alleles Celiac Disease/genetics Chromosome Aberrations Chromosome Deletion Complement C4/genetics DNA/genetics DNA Restriction Enzymes Deoxyribonucleases, Type II Site-Specific Genes Haploidy Humans Major Histocompatibility Complex Multiple Sclerosis/genetics Nucleic Acid Hybridization Phenotype Polymorphism, Genetic Steroid 21-Hydroxylase/genetics Steroid Hydroxylases/genetics
Chemicals
Complement C4 DNA Steroid Hydroxylases Steroid 21-Hydroxylase DNA Restriction Enzymes Deoxyribonucleases, Type II Site-Specific TCGA-specific type II deoxyribonucleases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Schneider P M
Carroll M C
Alper C A
Rittner C
Whitehead A S
Yunis E J
Colten H R
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42 references, click to expand
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI112623
Published
1986-09-00
Pages
650-7
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC423642
Subset
IM
Grants
NIAID NIH HHS · AI-21157 · United States
NICHD NIH HHS · HD-17461 · United States
NHLBI NIH HHS · HL-29583 · United States
External Links
PubMed source DOI: 10.1172/JCI112623 PMC Full Text View journal details
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