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PMID: 2788573 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Pulsed field gel electrophoresis identifies a high degree of variability in the number of tandem 21-hydroxylase and complement C4 gene repeats in 21-hydroxylase deficiency haplotypes.

The EMBO journal ·Vol. 8 ·No. 5 ·1989-05-00 ·Pages 1393-402

Collier S, Sinnott PJ, Dyer PA, Price DA, Harris R, Strachan T

Abstract

The human steroid 21-hydroxylase gene, CYP21B, and its closely homologous pseudogene, CYP21A, are each normally located centromeric to a complement C4 gene C4B and C4A respectively, in an organization suggesting tandem duplication of a CYP21 + C4 unit. Such an organization has been considered to facilitate gene deletion and addition events by unequal crossover between the tandem repeats. However, the large size (approximately 30 kb) of the individual CYP21 + C4 repeat units together with the difficulty in identifying reliable CYP21A- and CYP21B-specific markers has prevented direct monitoring of gene organization on individual haplotypes by conventional Southern analyses. In the present investigation we have sought to clarify the CYP21 and C4 gene organization in members of 32 British 21-hydroxylase deficiency families by employing additional experimental approaches, notably a long-range restriction mapping approach, which permits assessment through a VNTR type of analysis, of the number of CYP21 and C4 units on individual haplotypes. Our results show that there is a very high frequency (33%) of 21-hydroxylase deficiency haplotypes where functional CYP21B gene sequence has been removed as a consequence of CYP21 + C4 gene deletion while several haplotypes show evidence of gene addition. In each case that we have investigated the gene deletion and gene addition haplotypes differ in length from conventional haplotypes by integral multiples of approximately 30 kb, which strongly supports the involvement of unequal crossover mechanisms. Additionally, the comparatively frequent occurrence of CYP21 fusion genes which contain both CYP21A- and CYP21B-associated markers is suggested by the combined data from Southern analyses, long-range restriction mapping and characterization of selected regions of CYP21 genes which have been amplified in vitro.

MeSH Terms
Adrenal Hyperplasia, Congenital Chromosome Deletion Complement C4/genetics Crossing Over, Genetic Electrophoresis, Agar Gel Female HLA Antigens/genetics Haplotypes Humans Male Mutation Pedigree Pseudogenes Repetitive Sequences, Nucleic Acid Restriction Mapping Steroid 21-Hydroxylase/genetics Steroid Hydroxylases/genetics
Chemicals
Complement C4 HLA Antigens Steroid Hydroxylases Steroid 21-Hydroxylase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Collier S
University Department of Medical Genetics, St Mary's Hospital, Manchester, UK.
Sinnott P J
Dyer P A
Price D A
Harris R
Strachan T
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1989-05-00
Pages
1393-402
Language
English
Region
England
NLM ID
8208664
PMCID
PMC400966
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source PMC Full Text View journal details
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