Vol. 12, Issue 12, 1885-1888, December 2002

LETTER
A Nonsense Mutation in the FMO3 Gene Underlies Fishy Off-Flavor in Cow's Milk

Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden

Fish-odor syndrome or Trimethylaminuria (OMIM #602079) in humans is an inborn error of metabolism associated with a characteristic fishy body odor due to elevated levels of trimethylamine (TMA) in body fluids. It is caused by loss-of-function mutations in FMO3 encoding flavin-containing mono-oxygenase 3. A fishy off-flavor is occasionally observed in cow's milk and it has been established recently that this phenotype is due to elevated TMA levels. Here, we report that fishy off-flavor in cow's milk is caused by a nonsense mutation (R238X) in the bovine FMO3 ortholog. RT-PCR analysis indicated that the mutant transcript is present in a very low amount. The mutation was found to be surprisingly common (q = 0.155) in one breed of cattle.

[The sequence data described in this paper have been submitted to GenBank with accession nos. AF488417-AF488422. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: K. Sandberg and I. Hansson.]