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International Team Publishes Analyses of Cattle Genome

NEW YORK (GenomeWeb News) – A research team involving hundreds of scientists from dozens of countries has finished sequencing the domestic cattle genome — and started unraveling its patterns of genetic variation. The work is being published in two papers appearing online today in Science. Another 20 companion reports are being published through BioMed Central.

The Bovine Sequencing and Analysis Consortium and Bovine HapMap Consortium sequenced and analyzed the genome of a Hereford cow and developed probes to assess patterns of genetic variation across hundreds of cattle from 19 breeds. Their results are shedding light on the genetic bases of several important agricultural traits such as cattle evolution, health and disease resistance, and meat and milk production.

"Understanding the cattle genome and having the sequence will allow researchers to understand the genetic basis for disease in domestic cattle and could result in healthier production of meat and milk while reducing producers' dependence on antibiotics," Agriculture Secretary Tom Vilsack said in a statement.

"Genetic tools are already being developed and proving useful to the dairy industry and we predict that they will be applied to improve the beef industry," Richard Gibbs, director of the Baylor College of Medicine Human Genome Sequencing Center Director, said in a statement. Gibbs led the Bovine Sequencing and Analysis Consortium and co-led the Bovine HapMap Consortium.

Along with the implications for improving milk and meat production, food safety, and the environmental impact of cattle, researchers say the domestic cattle genome is helping to inform cattle biology and mammalian evolution and may eventually lead to better tools for understanding human health and disease.

cow2.jpg"The domestic cattle genome sequence opens another window into our own genome," acting National Institutes of Health Director Raynard Kington, who was not directly involved with the project, said in a statement. "By comparing the human genome to the genomes of many different species, such as the domestic cattle, we can gain a clearer view of how the human genome works in health and in disease."

The six-year sequencing project was funded by the US Department of Agriculture, the National Institutes of Health, Genome Canada, the Australian Commonwealth Scientific and Research Organization, the Research Council of Norway, as well as several other national, state, and provincial organizations around the world. The final cost of the project was not disclosed.

Researchers sequenced the roughly 2.87 billion base pair genome of a female Hereford to about seven-fold coverage. Data from bacterial artificial chromosome and whole-genome shotgun sequences were combined to come up with the two most recent cattle genome assemblies, Btau3.1 and Btau4.0.

The team's analysis suggests that the cow's 29 chromosome pairs and X-chromosome contain 22,000 protein-coding genes, roughly 500 microRNA genes, and ruminant-specific repeats that make up about 27 percent of the cattle genome.

When the team compared the domestic cattle genome with human, dog, mouse, rat, opossum, and platypus genomes, they found 14,345 orthologous gene groups shared between cattle and other mammals. They also discovered 1,217 orthologous groups that were only shared between placental mammals.

As a whole, the researchers found that human genome organization more closely resembles the cattle genome than that of rats or mice. Even so, the researchers found roughly 1,000 genes present in cattle, rodent, and dog genomes that were not in the human genome. And while most metabolic genes were conserved in the cattle genome, five were missing or had changed dramatically compared to humans.

The team's analyses also suggest that the cattle genome has undergone numerous rearrangements, spurred by repetitive elements and duplications such as segmental duplication, retrotransposons, and retroviral long terminal repeats. For example, they found 1,020 segmental duplications involving more than three percent of the genome.

In particular, the cattle genome contained duplications in genes involved in immune function, olfactory receptors, reproduction, lactation, and digestion. Ten immune system-related genes were also among the 71 genes under positive selection in the domestic cow genome.

In a second paper, researchers from the Bovine HapMap Consortium described their efforts to characterize genetic diversity in different cattle breeds. Based on the Hereford genome sequence, along with comparative sequences from Holstein, Angus, Jersey, Limousin, Norwegian Red, and Brahman breeds, the team identified 37,470 SNPs that they subsequently evaluated in nearly 500 cattle from 19 breeds.

Overall, indicine cattle, humped cattle found in South Asia and East Africa, had higher SNP diversity than taurine cattle, humpless cattle found in Europe, Africa, Asia, and elsewhere. For instance, Brahman cattle had a SNP every 285 base pairs — the highest level of genetic diversity observed in cattle breeds so far. Holstein and Angus breeds had about half as many SNPs.

The team identified specific regions of the genome associated with traits such as milk yield, meat quality, and disease or pest resistance — traits that have been selected through cattle breeding programs. But, they warned, the HapMap data reveals evidence of bottlenecks in cattle populations following domestication.

"The bovine HapMap data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation," University of Missouri researcher Jerry Taylor, who was part of the Bovine HapMap team, said in a statement. "The recent decline in diversity is sufficiently rapid that loss of diversity should be of concern to animal breeders."

University of Illinois at Urbana-Champaign Institute for Genomic Biology Director Harris Lewin, who led two teams involved in cattle genome sequencing, echoed this sentiment in a perspectives article appearing in the same issue of Science. Lewin noted that the apparent links between animal breeding and genomic architecture suggest that "genetic diversity should be carefully monitored as genomic selection for quantitative traits takes its place as a routine technology for animal genetic improvement."

"Comparisons of the cattle genome to that of other mammals [were] ... expected to yield exciting new information on how mammalian genomes evolve, mechanisms of gene regulation, genetic control of complex traits, and host-microbe interactions," Lewin wrote. "The cows have not disappointed us."

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