Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity
- Univ. of North Carolina, Chapel Hill (USA)
- Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA)
Androgens act through a receptor protein (AR) to mediate sex differentiation and development of the male phenotype. The authors have isolated the eight exons in the amino acid coding region of the AR gene from a human X chromosome library. Nucleotide sequences of the AR gene intron/exon boundaries were determined for use in designing synthetic oligonucleotide primers to bracket coding exons for amplification by the polymerase chain reaction. Genomic DNA was amplified from 46, XY phenotypic female siblings with complete androgen insensitivity syndrome. AR binding affinity for dihydrotestosterone in the affected siblings was lower than in normal males, but the binding capacity was normal. Sequence analysis of amplified exons demonstrated within the AR steroid-binding domain (exon G) a single guanine to adenine mutation, resulting in replacement of valine with methionine at amino acid residue 866. As expected, the carrier mother had both normal and mutant AR genes. Thus, a single point mutation in the steroid-binding domain of the AR gene correlated with the expression of an AR protein ineffective in stimulating male sexual development.
- OSTI ID:
- 6855341
- 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. 86:23; ISSN 0027-8424; ISSN PNASA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ADENINES
AMINES
ANDROGENS
ANDROSTANES
ANTIMETABOLITES
AROMATICS
AZAARENES
CELL DIFFERENTIATION
CHROMOSOMES
DNA BASE TRANSITIONS
DNA SEQUENCING
DRUGS
GENE AMPLIFICATION
GENE MUTATIONS
GUANINE
HETEROCHROMOSOMES
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROXY COMPOUNDS
MEMBRANE PROTEINS
MUTATIONS
NUCLEIC ACIDS
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHENOTYPE
PROTEINS
PURINES
RECEPTORS
STEROID HORMONES
STEROIDS
STRUCTURAL CHEMICAL ANALYSIS
X CHROMOSOME