The STR system in the human phenylalanine hydroxylase gene: true fragment length obtained with fluorescent labelled PCR primers

Zschocke, Johannes; Graham, Colin A.; McKnight, J.J.; Nevin, N. C.

doi:10.1111/j.1651-2227.1994.tb13447.x

Cited by 16 publications

(13 citation statements)

References 1 publication

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“…VNTR and STR polymorphisms were analysed through PCR amplification and visualisation on 3% NuSieve (FMC) agarose gels or a fluorescent DNA analysis system, respectively. STR allele size is denoted as previously described [Zschocke et al, 1994]. Three of the seven original RFLPs for haplotyping (BglII, PvuIIb and MspI) were analysed by PCR amplification and restriction digest.…”

Section: Methodsmentioning

confidence: 99%

The molecular basis of phenylalanine hydroxylase deficiency in Croatia

et al. 2003

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We present the results of a comprehensive analysis of mutations, polymorphisms and haplotypes in the phenylalanine hydroxylase ( PAH) gene in 39 Croatian families with phenylketonuria (PKU). A total of 21 disease-causing mutations was identified on 78 out of 79 independent chromosomes. The commonest mutation, R408W on haplotype 2 was found with a relative frequency of 37 %. P281L accounted for 11 %, R261Q and E390G each for 9 % of mutant chromosomes. There were three novel mutations: L249P (c.746T>C) in exon 7, IVS8+2T>C (c.912T>C) in intron 8, and F402L (c.1206T>G) in exon 12 of the PAH gene. Two known PKU mutations were found in cis on the same chromosome in one family, highlighting the need to perform full mutation scanning in recessive disease genes for molecular diagnosis even if two known mutations have been identified in a patient. This is the first comprehensive report on PKU mutations in southeastern Europe, adding to the growing bulk of molecular data for population genetic investigations.

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Section: Methodsmentioning

confidence: 99%

The molecular basis of phenylalanine hydroxylase deficiency in Croatia

et al. 2003

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“…STR genotypes were determined by PCR amplification and allele sizing by electrophoresis on the ABI 310 automated sequencer. 9,33 Results DNA samples from 279 unrelated hyperphenylalaninaemia cases, equivalent to 558 PAH alleles, were screened by DGGE for the presence of mutation in the 13 exons of the PAH gene. Electrophoretic mobility shifts, indicative of base sequence alteration, were detected for all except 24 (4.3%) alleles.…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

The mutation spectrum of hyperphenylalaninaemia in the Republic of Ireland: the population history of the Irish revisited

O’Donnell

O’Neill²,

Tighe

et al. 2002

Eur J Hum Genet

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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.

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“…PAH tetranucleotide STR genotypes were determined according to the protocol of Zschocke et al [1994] by PCR amplification and allele sizing by electrophoresis on an ALFexpress automated sequencer (Amersham Biosciences, Little Chalfont, UK). STR associations with VNTR genotypes were determined for 146 of 184 alleles (79%).…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

Genetic diversity within the R408W phenylketonuria mutation lineages in Europe

et al. 2003

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For the PKU Special IssueThe R408W phenylketonuria mutation in Europe has arisen by recurrent mutation in the human phenylalanine hydroxylase (PAH) locus and is associated with two major PAH haplotypes. R408W-2.3 exhibits a west-to-east cline of relative frequency reaching its maximum in the Balto-Slavic region, while R408W-1.8 exhibits an east-to-west cline peaking in Connacht, the most westerly province of Ireland. Spatial autocorrelation analysis has demonstrated that the R408W-2.3 cline, like that of R408W-1.8, is consistent with a pattern likely to have been established by human dispersal. Genetic diversity within wild-type and R408W chromosomes in Europe was assessed through variable number tandem repeat (VNTR) nucleotide sequence variation and tetranucleotide short tandem repeat (STR) allelic associations. Wild-type VNTR-8 chromosomes exhibited two major cassette sequence organizations: (a1) 5 -b3-b2-c1 and (a1) 5 -b5-b2-c1. R408W-1.8 was predominantly associated with (a1) 5 -b5-b2-c1. Both wild-type VNTR-3 and R408W-2.3 chromosomes exhibited a single invariant cassette sequence organization, a2-b2-c1. STR allele distributions associated with the cassette variants were consistent with greater diversity in the wild-type VNTR-8 lineage and were suggestive of different levels of diversity between R408W-1.8 and R408W-2.3. The finding of greater genetic diversity within the wild-type VNTR-8 lineage compared to VNTR-3 suggests that VNTR-8 may be older within the European population. However, in the absence of a more extensive STR data-set, no such conclusions are possible for the respective R408W mutant lineages. Hum Mutat 21:387-393,

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The STR system in the human phenylalanine hydroxylase gene: true fragment length obtained with fluorescent labelled PCR primers

Cited by 16 publications

References 1 publication

The molecular basis of phenylalanine hydroxylase deficiency in Croatia

The molecular basis of phenylalanine hydroxylase deficiency in Croatia

The mutation spectrum of hyperphenylalaninaemia in the Republic of Ireland: the population history of the Irish revisited

Genetic diversity within the R408W phenylketonuria mutation lineages in Europe

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