A functional analysis of disease-associated mutations in the androgen receptor gene.
Mutations in the androgen receptor (AR) are associated with a variety of diseases including androgen insensitivity syndrome and prostate cancer, but the way in which these mutations cause disease is poorly understood. We present a method for distinguishing likely disease-causing mutations from mutations that are merely associated with disease but have no causal role. Our method uses a measure of nucleotide conservation, and we find that conservation often correlates with severity of the clinical phenotype. Further, by only including mutations whose pathogenicity has been proven experimentally, this correlation is enhanced in the case of prostate cancer-associated mutations. Our method provides a means for assessing the significance of single nucleotide polymorphisms (SNPs) and cancer-associated mutations.
Mooney
Sean D
SD
Stanford Medical Informatics, Department of Genetics, Stanford University, MSOB X-215, 251 Campus Drive, Stanford, CA 94305-5479, USA. sdm@stanford.edu
Klein
Teri E
TE
Altman
Russ B
RB
Trifiro
Mark A
MA
Gottlieb
Bruce
B
D000465:Algorithms; D013734:Androgen-Insensitivity Syndrome / Q000235:genetics* / Q000473:pathology; D001665:Binding Sites / Q000235:genetics; D030561:Databases, Nucleic Acid; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009154:Mutation; D011944:Receptors, Androgen / Q000235:genetics*; D016415:Sequence Alignment; D012720:Severity of Illness Index
D011944:Receptors, Androgen