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Mapping the pig genome
By Lone Frank

According to the ancient Chinese calendar, 2000 is the year of the dragon, but for a group of Beijing scientists it feels like the year of the pig. In the Chinese capital the Human Genome Center is gearing up to sequence the genome of the pig and hopes to join forces with Danish colleagues.

"This collaboration makes perfect sense," says geneticist Huanming Yang, director of the Beijing Institute of Genetics. He explains half jokingly that "while China is the world leader in producing and consuming pigs, Denmark produces the most pigs per capita." But jokes aside, two compelling reasons make the pig genome worth mapping—agriculture and research on human disease.

"The pig is of major economic importance to both Denmark and China, but also many third-world countries have great interest in breeding better strains," says geneticist Torben Greve of Copenhagen's Agricultural University. He is currently involved in getting together a consortium of Denmark's experts on pig genetics and raising funds for the Sino-Danish sequencing effort. One valuable asset brought to the table by the Chinese is the country's unique collection of native pig strains, many of which are naturally resistant to disease. "For breeding purposes, the genes responsible for various resistances as well as genes that influence meat quality are highly interesting," says Yang, who has a two-pronged plan. While a pig strain common to both China and Europe will be completely sequenced as 'reference genome,' genetic variants from several other strains will be characterized for comparison.

Recent computer modeling at Denmark's Foulom Agricultural Research Center has revealed many common pig diseases to be partly or completely inherited. Identifying disease-causing variants may make it possible to selectively breed them out, predicts veterinarian Merete Fredholm of the Danish Agricultural University. As part of a European pig genetics project, she is hunting for a gene that kills millions of pigs each year by making them susceptible to the deadly E. coli. "We have pinpointed the gene to a chromosomal region, but having sequence data would allow us to quickly zoom in on the gene and clarify its function," she says.

In terms of size, the pig genome compares with the human genome

According to geneticist Lars Bolund of Aarhus University, many researchers hope that better knowledge of pig genetics will give the animal a more prominent role in human disease research. With a physiology very close to human, the pig is valuable for investigating organ function especially in the urinary, cardiovascular and nervous systems. And there is general interest in creating transgenic pig disease models, physiologist Jørgen Frøkjær of Aarhus University Hospital points out. "We anticipate they would be superior to the existing rodent models which often don't reflect the full range of symptoms." An important point of the genomic sequence, adds Frøkjær, is that it promises a better understanding of disease processes by allowing scientists to study expression patterns of whole arrays of selected genes under various conditions.

A full view of the pig genome could also help researchers interested in using pig organs for xenotransplantation in human patients. Tissue-type genes are of particular interest, says Yang, because "a better understanding of what makes pig tissue incompatible with the human organism provides a basis of producing transgenic animals that do not express genes causing rejection."

In terms of size, the pig genome compares with our own. A network of mainly European research groups has already established a physical map staking out the relative position of many genes and, according to Yang, "leaning on this map and using the working draft of the human sequence as a reference will allow us to complete the project within the next two years." Clearly, technical facilities are not an issue. Today Yang commands a small army of 230 scientists and 70 bioinformatics specialists and the Beijing center's sequencing capacity of 3 megabases per day is expected to double before the end of this year.

Official China seems to have gone the whole hog on genomics. The government has enthusiastically supported Yang's institute, which proved its abilities by participating in the international Human Genome Project and sequencing areas of chromosome 3 corresponding to 1 percent of the entire human sequence. Sequencing the pig genome is the first large-scale project to come out of a developing country, and Yang is confident that "it will give a great boost to Chinese genomics and genetics research." China also hopes to feel a positive economic impact of this new science. Right next to Yang's public institute a research park has recently shot up to welcome international collaborations and accommodate biotech industry.

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