title: The mutation spectrum of hyperphenylalaninaemia in the Republic of Ireland: the population history of the Irish revisited.
abstract: Phenylketonuric and hyperphenylalaninaemic patients in the population of the Republic of Ireland were screened for mutations at the human phenylalanine hydroxylase (PAH) locus. A composite data set for the island of Ireland was generated by merging the findings of this study with extant data for Northern Ireland. Analysis of this data on the basis of the four historic provinces (Munster, Leinster, Connacht and Ulster) revealed genetic diversity that is informative in terms of demographic forces that shaped the Irish population. R408W, the predominant Irish PAH mutation associated with haplotype 1.8, reached its highest relative frequency in the most westerly province, Connacht. This suggests that the gradient of R408W-1.8 observed across north-western Europe continues into Ireland and peaks in Connacht. Spatial autocorrelation analysis demonstrated that the gradient is consistent with a localised cline of R408W-1.8 likely to have been established by human migration. This and parallel allele frequency clines may represent the genetic traces of the Palaeolithic colonisation of Europe, a pattern not substantially altered in north-western Europe by subsequent Neolithic migrations. An analysis of mutant allele distributions in Ulster, Scotland and the rest of Ireland confirmed that Ulster has been a zone of considerable admixture between the Irish and Scottish populations, indicating a proportion of Scottish admixture in Ulster approaching 46%. Mutations primarily associated with Scandinavia accounted for 6.1% of mutations overall, illustrating the influence of Viking incursions on Irish population history.
authors.affiliation: Department of Pathology, The Children's Hospital, Temple Street, Dublin 1, Republic of Ireland.
authors.forename: Kate A
authors.initials: KA
authors.lastname: O'Donnell
authors.forename: Charles
authors.initials: C
authors.lastname: O'Neill
authors.forename: Orna
authors.initials: O
authors.lastname: Tighe
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bertorelle
authors.forename: Eileen
authors.initials: E
authors.lastname: Naughten
authors.forename: Philip D
authors.initials: PD
authors.lastname: Mayne
authors.forename: David T
authors.initials: DT
authors.lastname: Croke
mesh_terms: D019943:Amino Acid Substitution; D003433:Crosses, Genetic; D005091:Exons; D005787:Gene Frequency; D005828:Genetics, Population; D005843:Geography; D006801:Humans; D007494:Ireland; D009154:Mutation; D009660:Northern Ireland; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012606:Scotland
chemical_list: D010651:Phenylalanine Hydroxylase