A role for overdominant selection in phenylketonuria? Evidence from molecular data

Hum Mutat. 2003 Apr;21(4):394-7. doi: 10.1002/humu.10205.


To date, the reason is unknown for the high prevalence of phenylalanine hydroxylase (PAH) mutations causing phenylketonuria (PKU) in extant European populations. However, 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"). Such selection would have acted upon several different mutations in different historical populations. The exact nature of the underlying selective mechanism is unknown; its elucidation requires further investigation.

Publication types

  • Review

MeSH terms

  • Evidence-Based Medicine / methods*
  • Genes, Dominant / genetics*
  • Genetics, Population / methods
  • Genetics, Population / statistics & numerical data
  • Humans
  • Phenylalanine Hydroxylase / genetics
  • Phenylketonurias / enzymology*
  • Phenylketonurias / genetics*
  • Selection, Genetic*


  • Phenylalanine Hydroxylase