Phenylketonuria as a balanced polymorphism: the nature of the heterozygote advantage

@article{Woolf1975PhenylketonuriaAA,
  title={Phenylketonuria as a balanced polymorphism: the nature of the heterozygote advantage},
  author={Louis I. Woolf and M S McBean and F. M. Woolf and S. F. Cahalanf},
  journal={Annals of Human Genetics},
  year={1975},
  volume={38}
}
Mothers of children with phenylketonuria have a significantly lower miscarriage rate than a matched control population in Ireland and west Scotland. This protective effect of the gene against some factor causing foetal death would seem to constitute a heterozygote advantage which might account for the previously observed polymorphism for phenylketonuria. It is suggested that the decrease in foetal mortality is mediated by the higher concentration of phenylalanine in the heterozygous mother's… 
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38 Citations
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38 Citations

Influence of the phenylketonuric heterozygote on the developing fetus
TLDR
Analysis of mental development scores in 82 non-PKU children age 3–14 years born to heterozygous mothers revealed normal values of psychometric tests.
Heterozygote advantage for the phenylketonuria allele.
TLDR
Heterozygote advantage presumably explains the presence of the allele at frequencies above those to be expected from the simple replacement of a homozygously-lethal allele by mutation alone.
Heterozygote advantage for the phenylketonuria allele.
TLDR
Heterozygote advantage presumably explains the presence of the allele at frequencies above those to be expected from the simple replacement of a homozygously-lethal allele by mutation alone.
A role for overdominant selection in phenylketonuria? Evidence from molecular data
TLDR
Molecular genetic data generated over the last decade suggest that the concomitant excess of (unaffected) PKU carriers is at least in part the result of overdominant selection (“heterozygous advantage”).
Phenylketonuria from genetics to clinics: An Iranian prospect
TLDR
Clinical and molecular basis of the PKU disease, with emphasis on the studies performed in Iranian population, were reviewed and investigated toward the elucidation of molecular aspects of the disease.
A method for analysing fertility of heterozygotes for autosomal recessive disorders, with special reference to cystic fibrosis, Tay‐Sachs disease and phenylketonuria
TLDR
A method has been developed which offers a better approach to the study of heterozygotes fertility in those autosomal recessive conditions which lack a test for direct heterozygote detection.
A single origin of phenylketonuria in Yemenite Jews
TLDR
It is reported that a single molecular defect—a deletion spanning the third exon of the PAH gene—is responsible for all the PKU cases among the Yemenite Jews.
Birth weight and pathogenesis in phenylketonuria.
TLDR
The results do not provide support for the "justification" hypothesis that the mental and neurological defects in phenylketonuria result from prenatal tyrosine deprivation which would be reflected in lower birthweights.
The PAH gene, phenylketonuria, and a paradigm shift
TLDR
The PKU story contains many messages, including: a framework on which to appreciate the complexity of PKU in which phenotype reflects both locus‐specific and genomic components; what the human PAH gene tells us about human population genetics and evolution of modern humans; and how the interest in PKU is served by a locus-specific mutation database.
The high frequency of phenylketonuria in Ireland and Western Scotland
  • L. Woolf
  • Medicine
    Journal of Inherited Metabolic Disease
  • 2005
TLDR
The PKU gene frequency and the incidence of the disease may be rising in Ireland and Western Scotland; the rates of rise can be calculated from the equation in Table 2.
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References

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