Codon-usage variants in the polymorphic (GGN) _n trinucleotide repeat of the human androgen receptor gene

Abstract

The human androgen receptor gene (hAR) has a long, polymorphic trinucleotide (GGN; glycine) _n repeat in the 3′ portion of its first exon, with n = 10–31. Owing to technical difficulties that have precluded routine sequencing of this region, it is widely unknown that N represents T, G or C, and that the usual sense codon sequence of the GGN tract is (GGT)₃GGG(GGT)₂(GGC)_4–25. Furthermore, on 4 of 61 X chromosomes, we observed that the internal GGT sequence was present three or four times instead of twice. Strikingly, each of the three alleles with an internal (GGT)₃, and only these three, also had a (GGC)₂₀ repeat. The size or composition of a (GGN) _n repeat was not correlated with the length of the accompanying (CAG) _n CAA repeat in the 5′ portion of exon one. Hence, codon-usage variants of the GGN tract may be used to seek associations with particular diseases, as diagnostic aids in families with androgen insensitivity whose AR mutations have not yet been identified, or as internal controls for observations on intergenerational contractions or expansions of the (CAG) _n CAA tract in a given hAR allele.