title: Structural analysis of the chimeric CYP21P/CYP21 gene in steroid 21-hydroxylase deficiency.
abstract: Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase (CYP21) gene. More than 90% of CAH cases are caused by mutations of the CYP21 gene. Approximately 75% of the defective CYP21 genes are generated through intergenic recombination, termed "apparent gene conversion," from the neighboring CYP21Ppseudogene. A chimeric CYP21P/CYP21gene with its 5' end corresponding to CYP21P and 3' end corresponding to CYP21 has been identified. This type of gene is nonfunctional because it produces a truncated protein. We found two distinct chimeric genes in CAH patients. Both genes had a sequence with -300 nucleotides of the 5' head as the CYP21P gene. The coding region consisted of a fusion molecule with the CYP21P gene in two different regions. One of the junctions was located in the chi-like sequence of GCTGGGC in the third intron and the other was in the minisatellite consensus TGGCAGGAGG of exon 5 of the CYP21P gene. In addition, analysis of restriction fragment length polymorphism for these two 3.3-kb chimeric molecules showed that these sequences arose as a consequence of unequal crossover between the CYP21Pand CYP21 genes. It is plausible that both consensus sequences are responsible for the gene conversion of these two chimeric genes.
authors.affiliation: King Car Food Industrial Co, Ltd, Yuan-Shan Research Institute, Taiwan, Republic of China. hhlee@ms2.kingcar.com.tw
authors.forename: Hsien-Hsiung
authors.initials: HH
authors.lastname: Lee
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
authors.forename: Ruey-Wen
authors.initials: RW
authors.lastname: Lin
authors.forename: Peter
authors.initials: P
authors.lastname: Chan
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Lin
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology / Q000235:genetics*; D000483:Alleles; D002678:Chimera / Q000235:genetics; D003434:Crossing Over, Genetic; D004252:DNA Mutational Analysis; D005785:Gene Conversion; D006801:Humans; D018598:Minisatellite Repeats / Q000235:genetics*; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D011544:Pseudogenes; D017422:Sequence Analysis, DNA; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: D013255:Steroid 21-Hydroxylase