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Scientists pinpoint gene linked to fat in cow’s milk
Edward R. Winstead


Scientists have identified a genetic mutation in dairy cows that appears to increase the fat content in milk by about a half percent. The discovery comes four years after researchers reported that cows with the higher levels of milk fat have one or several genes in common on chromosome 14. In the new study, researchers pinpointed a single mutation on chromosome 14 that appears to be responsible for changing the composition of the milk.

Holstein-Friesian cow.

Michel Georges, of the Faculty of Veterinary Medicine at the University of Liege, Belgium, led the study. His team used comparative genomics to locate the gene, called DGAT1. They assembled short DNA sequences from cow chromosome 14 and compared them to the nearly complete corresponding sequence of the human genome. The comparison showed that the cow DGAT1 gene resides in the implicated region on cow chromosome 14.

The DGAT1 gene was immediately the prime suspect for two reasons. It encodes an enzyme that catalyzes the final step in the synthesis of triglycerides, which make up about 98 percent of fats in milk. Furthermore, mice lacking the DGAT1 gene do not produce milk. This led the researchers to hypothesize that the cow version was involved in the composition of cow's milk. They screened the gene in two herds of Holstein-Friesian populations and identified variants, including the mutation.

The study is part of ongoing research to understand why some cows produce a different type and more milk than others. "Most of the traits we are studying appear to reflect the effects of several linked genes," says Georges. "But in this case we think that DGAT1 is the only gene responsible for the effect. The current study may be simpler than what we will face in the future."

His laboratory undertook biochemical and genetic studies to confirm the mutation's role in the trait. They published their circumstantial evidence implicating DGAT1 in the effect in Genome Research. The increased fat yield was identified in distant and diverse herds, suggesting that the mutation is relatively old.

"This is one of the first apparent successes in mapping traits, and certainly in the field of cattle genetics," says James E. Womack, of the College of Veterinary Medicine at Texas A&M University. Womack and others are developing a new comparative map of the human and cattle genomes to be released later this year. His team recently published a new comparative map of cow chromosome 18; the map shows that this chromosome basically consists of parts of two human chromosomes.

"We've been building these comparative maps for years hoping they would be useful for finding genes for traits," says Womack. "It is gratifying to see that we are beginning to find genes responsible for traits that have economic value."

Documenting evolutionary relationships among mammals reveals something about how genomes have evolved. This is of biological interest to some researchers, but there is also a practical aspect. The sites of chromosome rearrangements, called evolutionary breakpoints, are key landmarks that allow researchers to line up sequences and pull out genes.

"I'm happy to see that this evolutionary history of chromosomes has turned out to be extremely useful," says Womack, noting that many people had told him the work was esoteric and he was wasting his time. "The comparative maps allow us to extrapolate from one genome to another, and we can benefit from the work done in human and mouse with a high-resolution comparative map."

See related "In the Literature" Mapping traits in farm animals.

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Grisart, B. et al. Positional candidate cloning of a QTL in dairy cattle: Identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition. Genome Res 12, 222-231 (February 2002).
Goldammer, T. et al. A comparative radiation hybrid map of bovine chromosome 18 and homologous chromosomes in human and mice. Proc Natl Acad Sci USA 99, 2106-2111 (February 19, 2002).
Band, M.R. et al. An ordered comparative map of the cattle and human genomes.
Genome Res 10, 1359-1368 (September 2000).
Ron, M. et al. Detection and analysis of a locus affecting milk concentration in the US and Israeli dairy cattle populations. Proc. 6th World Congress on Genetics Applied to Livestock Production, Armidale, Australia. 26, 422-425 (1998).

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