A nonsense mutation in the FMO3 gene underlies fishy off-flavor in cow's milk

Abstract

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.

Figure 1

(A) Alignment of codon 236–238 for the normal (R238) and mutant (R238X) FMO3 allele in cattle. This region was analyzed using pyrosequencing. The location of the sequencing primer and the six positions sequenced are indicated. (B) Pyrosequencing results from the three different genotypes at codon 238. The sequenced reverse strand has the sequence (A/G)AGTGA, in which the A/G polymorphism corresponds to the R238X nonsense mutation.