Genesis by meiotic unequal crossover of a de novo deletion that contributes to steroid 21-hydroxylase deficiency

Journal Article · Thu Mar 01 04:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.6.2107· OSTI ID:6072038

Sinnott, P; Collier, S; Dyer, P A; Harris, R; Strachan, T ^[1]; Costigan, C ^[2]

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1. Saint Mary's Hospital, Manchester (England)
2. Our Lady's Hospital for Sick Children, Dublin (Ireland)

The HLA-linked human steroid 21-hydroxylase gene CYP21B and its closely homologous pseudogene CYP21A are each normally located centromeric to a fourth component of complement (C4) gene, C4B and C4A, respectively, in an organization suggesting tandem duplication of a ca. 30-kilobase DNA unit containing a CYP21 gene and a C4 gene. Such an organization has been considered to facilitate gene deletion and addition events by unequal crossover between the tandem repeats. The authors have identified a steroid 21-hydroxylase deficiency patient who has a maternally inherited disease haplotype that carries a de novo deletion of a ca. 30-kilobase repeat unit including the CYP21B gene and associated C4B gene. This disease haplotype appears to have been generated as a result of meiotic unequal crossover between maternal homologous chromosomes. One of the maternal haplotypes is the frequently occurring HLA-DR3,B8,A1 haplotype that normally carries a deletion of a ca. 30-kilobase unit including the CYP21A gene and C4A gene. Haplotypes of this type may possible act as premutations, increasing the susceptibility of developing a 21-hydroxylase deficiency mutation by facilitating unequal chromosome pairing.

• OSTI ID: 6072038
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:6; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550401* -- Genetics-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CELL DIVISION
COMPLEMENT
DAYS LIVING RADIOISOTOPES
DISEASES
DNA HYBRIDIZATION
ELECTROPHORESIS
ENZYMES
GENE MUTATIONS
HEREDITARY DISEASES
HYBRIDIZATION
HYDROXYLASES
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAN
MEIOSIS
MUTATIONS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PATHOGENESIS
PATIENTS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PRIMATES
PROTEINS
RADIOISOTOPES
VERTEBRATES