Background: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder affecting 4-12% of reproductive women worldwide; characterized by chronic anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovaries on ultrasound scan. Ovarian androgen overproduction is the key pathophysiologic feature of PCOS. A number of genes encoding major enzymes of the androgen meta...

OBJECTIVE Length of a polymorphic cytosine-adenine-guanine (CAG) repeat in the androgen receptor (AR) may inversely correlate with AR activity. We have identified an association between short AR allelotypes and decreased survival in women with epithelial ovarian cancer. We hypothesize short AR allelotypes promote aggressive ovarian cancer phenotype through modulation of epidermal growth factor ...

Shorter alleles of a polymorphic [CAG](n) repeat in exon 1 of the androgen receptor (AR) have been associated with increased risk of prostate cancer and decreased risk of breast cancer. We prospectively assessed the association between the [CAG](n) repeat polymorphism in the androgen receptor and breast cancer risk among Caucasian women in a case-control study nested within the Nurses' Health S...

Trinucleotide repeat disorders are a heterogeneous group of diseases caused by the expansion, beyond a pathogenic threshold, of unstable DNA tracts in different genes. Sequence interruptions in the repeats have been described in the majority of these disorders and may influence disease phenotype and heritability. Spinal bulbar muscular atrophy (SBMA) is a motor neuron disease caused by a CAG tr...

A substantial body of evidence supports the identity of polyglutamine as the pathogenic agent in a variety of human neurodegenerative disorders where the mutation is an expanded CAG repeat. However, in apparent contradiction to this, there are several human neurodegenerative diseases (some of which are clinically indistinguishable from the 'polyglutamine' diseases) that are due to expanded repe...

OGG1 and MSH2/MSH3 promote CAG repeat expansion at Huntington's disease (HD) locusin vivo during removal of oxidized bases from DNA. CSB, a transcription-coupled repair (TCR) protein, facilitates repair of some of the same oxidative lesions. In vitro, a knock down CSB results in a reduction of transcription-induced deletions at CAG repeat tract. To test the role of CSB in vivo, we measured inte...

Mutant transcripts containing expanded CUG repeats in the untranslated region are a pathogenic factor in myotonic dystrophy type 1 (DM1). The mutant RNA sequesters the muscleblind-like 1 (MBNL1) splicing factor and causes misregulation of the alternative splicing of multiple genes that are linked to clinical symptoms of the disease. In this study, we show that either long untranslated CAG repea...

Recently, the effect of exposure to persistent organic pollutants (POPs) on sperm concentration was only seen in men with a short androgen receptor (AR) gene CAG repeat. In order to investigate whether these effects could be observed also in vitro, we tested the impact of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (4,4'-DDE) on 5α-dihydrotestoster...

We report on mutation screening and CAG repeat length analysis of the androgen receptor (AR) gene in 21 patients with hypospadias. The urethral meatus was located at the glandular region in six patients (glandular type), at the penile shaft in seven patients (penile type), and at the scrotal/perineal region in eight patients (scrotal/perineal type). Mutation screening was performed for exons 1-...