Each year, an estimated 30,000 people in Africa are diagnosed with the crippling muscle wasting disease known as sleeping sickness. But the problem is far worse for the dairy and meat-producing cattle upon which their lives depend, as an estimated 5 billion cows die of Nagana, the animal form of the disease. Now, scientists hope to generate heartier, disease-resistant cattle — and the discovery of two new genes reported this week could help with that goal.
“The two genes discovered in this research could provide a way for cattle breeders to identify the animals that are best at resisting disease,” said Stephen Kemp, a geneticist at the UK’s University of Liverpool, in a statement.
In 1989, Kemp set out to eradicate the tsetse fly-borne disease in cattle with a simple strategy: his team crossed typical farming cattle called zebus to related disease-resistant West African cattle known locally as N’damas. Then, the researchers looked for traits that conferred sleeping sickness in resistant cattle. But the classical genetic methods his team used to find disease-resistant traits proved inconclusive. Kemp and his colleagues discovered 10 segments of the genome that conferred resistance, but the regions were simply too large and contained far too many genes to pinpoint the exact loci responsible for resistance.
With the help of functional genomics, however, Kemp’s team has now pinpointed two potential resistance genes in these regions. Using microarrays, the researchers identified a suite of genes that were switched on or off after infection in the heartier N’dama cattle. And after resequencing two genes of interest integral to fighting infections — ARHGAP15, which regulates neutrophil function, and TICAM1, which regulates dendritic cell migration — they identified disease-resistant alleles that had likely evolved in these West African cattle breeds to protect them from the disease.
N’damas themselves aren’t particularly good at plowing fields or producing milk. But by crossing these two resistant alleles from N’damas into zebus, researchers hope to create cattle breeds that are both resistant to disease and commercially productive.
Meanwhile, New York University biochemist Jayne Raper is taking a different approach to creating heartier cattle. As highlighted in our January 2011 news feature, Raper is hoping to take a resistance gene called APOL1 found in primates and into insert it into African cattle to make genetically-engineered, sleeping sickness-resistant cattle.
Kemp’s strategy might be more politically palatable, however. As Sue Welburn, a molecular epidemiologist from the UK’s University of Edinburgh who studies sleeping sickness in Uganda, told Nature Medicine in January: “People are reluctant to accept anything transgenic.”
Image: Stamp Out Sleeping Sickness Campaign.