Abstract for presentation at 11th International Congress of Human Genetics

A single-nucleotide polymorphism in ABCC11 gene is the determinant of human earwax type

  • Dr Koh-ichiro Yoshiura, Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki Japan, Japan
  • Dr Takafumi Ishida, Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan, Japan
  • Prof Toshihisa Ishikawa, Department of Biomolecular Engineering, Graduate School of Bioscence and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan
  • Prof Katsushi Tokunaga, Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, Japan
  • Prof De-Sheng Linag, National Laboratory of Medical Genetics of China, Central South University, Changsha, China, China
  • Prof Kenji Hirayama, Department of Molecular Immnogenetics, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan, Japan
  • Prof Naruya Saito, Division of Population Genetics, National Institute of Genetics, Mishima, Japan, Japan
  • Norio Niikawa, Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki Japan, Japan

    • Human cerumen (earwax) is a classical dimorphic genetic trait consisting of wet and dry types. The wet-type phenotype is completely dominant to the dry type. Dry cerumen is frequently seen in East Asian populations, while wet cerumen is common in other populations. We previously mapped the earwax gene locus to the pericentromeric region of chromosome 16. Here we show that a single nucleotide polymorphism, c.538G>A (Gly180Arg), in the ABCC11 gene is responsible for determination of the human earwax type, i.e., “AA” genotype corresponds to dry cerumen and “GA” and “GG” genotypes to wet cerumen. Another rare mutation, a 27-bp deletion (3939-3965del27) in exon 29 of ABCC11, independent to c.538G>A, was also found in a few individuals of Asian ancestry. Functional assay demonstrated that LLC-PK1 cells transfected with the allele “A”-bearing ABCC11 show a lower effluxing activity for cyclic GMP than those with allele “G”. Furthermore, the allele “A” frequency shows striking north-south and east-west downward geographical gradient distributions with a peak in Northern Chinese and Koreans among worldwide populations. This, together with previous anthropogenetic and archaeological data, suggests that a G>A substitution occurred in North-east Asia and allele “A” thereafter spread all over the world including the New World. The c.538G>A is the first example of a DNA polymorphism that determines directly a visible human dimorphic genetic trait.

    Conference Organiser - ICMS Pty Ltd