RECURRENCE OF THE R408W MUTATION IN THE PHENYLALANINE-HYDROXYLASE LOCUS IN EUROPEANS

The relative frequency of the common phenylalanine hydroxylase (PAH) m utation R408W and its associations with polymorphic RFLP, VNTR, and sh ort-tandem-repeat (STR) sites in the PAH gene were examined in many Eu ropean populations and one representative North American population of defined European descent. This mutation was found to cluster in two r egions: in northwest Europe among Irish and Scottish peoples, and in e astern Europe, including the Commonwealth of Independent States. This allele was significantly less frequent in intervening populations. In eastern European populations, the R408W mutation is strongly associate d with RFLP haplotype 2, the three-copy VNTR allele (VNTR 3), and the 240-bp STR allele. In northwestern European populations, it is strongl y associated with RFLP haplotype 1, the VNTR allele containing eight r epeats (VNTR 8), and the 244-bp STR allele. An examination of the link age between the R408W mutation and highly polymorphic RFLP, VNTR, and STR haplotypes suggests that recurrence is the most likely mechanism t o account for the two different major haplotype associations of R408W in Europe.