Founder effect of a prevalent phenylketonuria mutation in the Oriental population

Journal Article · Fri Mar 15 00:00:00 EST 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.6.2146· OSTI ID:5014601

Wang, Tao ^[1]; Okano, Yoshiyuki; Eisensmith, R C; Harvey, M L; Woo, S L.C. ^[2]; Lo, W H.Y.; Yuan, Lifang ^[3]; Huang, Shuzhen; Zeng, Yitao ^[4]; Furuyama, Junichi ^[5]; Oura, Toshiaki ^[6]; Sommer, S S ^[7]

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1. Baylor College of Medicine, Houston, TX (United States) Chinese Academy of Medical Sciences, Beijing (China)
2. Baylor College of Medicine, Houston, TX (United States)
3. Chinese Academy of Medical Sciences, Beijing (China)
4. Shanghai Children's Hospital (China)
5. Hyogo College of Medicine, Nishinomiya (Japan)
6. Osaka Municipal Rehabilitation Center for the Disabled, Osaka (Japan)
7. Mayo Clinic/Foundation, Rochester, MN (United States)

A missense mutation has been identified in the human phenylalanine hydroxylase Chinese patient with classic phenylketonuria (PKU). A G-to-C transition at the second base of codon 413 in exon 12 of the gene results in the substitution of Pro{sup 413} for Arg{sup 413} in the mutant protein. This mutation (R413P) results in negligible enzymatic activity when expressed in heterologous mammalian cells and is compatible with a classic PKU phenotype in the patient. Population genetic studies reveal that this mutation is tightly linked to restriction fragment length polymorphism haplotype 4, which is the predominant haplotype of the PAH locus in the Oriental population. It accounts for 13.8% of northern Chinese and 27% of Japanese PKU alleles, but it is rare in southern Chinese (2.2%) and is absent in the Caucasian population. The data demonstrate unambiguously that the mutation occurred after racial divergence of Orientals and Caucasians and suggest that the allele has spread throughout the Orient by a founder effect. Previous protein polymorphism studies in eastern Asia have led to the hypothesis that northern Mongoloids represented a founding population in Asia. The results are compatible with this hypothesis in that the PKU mutation might have occurred in northern Mongoloids and subsequently spread to the Chinese and Japanese populations.

• OSTI ID: 5014601
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:6; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HEREDITARY DISEASES
MOLECULAR BIOLOGY
HYDROXYLASES
GENE MUTATIONS
ASIA
BIOLOGICAL EVOLUTION
DNA BASE TRANSITIONS
GEOGRAPHICAL VARIATIONS
HUMAN POPULATIONS
MUTAGENESIS
PATIENTS
PHENYLALANINE
PHOSPHORUS 32
RFLPS
AMINO ACIDS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
DAYS LIVING RADIOISOTOPES
DISEASES
ENZYMES
ISOTOPES
LIGHT NUCLEI
MUTATIONS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PHOSPHORUS ISOTOPES
POPULATIONS
RADIOISOTOPES
VARIATIONS
550401* - Genetics- Tracer Techniques